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Zhang X, Nguyen MH. Metabolic dysfunction-associated steatotic liver disease: A sexually dimorphic disease and breast and gynecological cancer. Metabolism 2025; 167:156190. [PMID: 40081614 DOI: 10.1016/j.metabol.2025.156190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/26/2025] [Accepted: 03/09/2025] [Indexed: 03/16/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a global public health and economic burden worldwide in the past few decades. Epidemiological studies have shown that MASLD is a multisystem disease that is associated not only with liver-related complications but also with an increased risk of developing extrahepatic cancers. MASLD is a sexually dimorphic disease with sex hormones playing an important role in the development and progression of MASLD, especially by the levels and ratios of circulating estrogens and androgens. MASLD is associated with hormone-sensitive cancers including breast and gynecological cancer. The risk of breast and gynecological cancer is elevated in individuals with MASLD driven by shared metabolic risk factors including obesity and insulin resistance. Multiple potential mechanisms underline these associations including metabolic dysfunction, gut dysbiosis, chronic inflammation and dysregulated release of hepatokines. However, the effect of hormone therapy including hormone replacement therapy and anti-estrogen treatment on MASLD and female-specific cancers remains debatable at this time. This synopsis will review the associations between MASLD and breast and gynecological cancer, their underlying mechanisms, implications of hormonal therapies, and their future directions.
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Affiliation(s)
- Xinrong Zhang
- Division of Gastroenterology and Hepatology, School of Medicine, Stanford University Medical Center, Palo Alto, CA, United States
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, School of Medicine, Stanford University Medical Center, Palo Alto, CA, United States; Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, United States; Stanford Cancer Institute, Stanford University Medical Center, Palo Alto, CA, United States.
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2
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Zhang JW, Zhang N, Lyu Y, Zhang XF. Influence of Sex in the Development of Liver Diseases. Semin Liver Dis 2025. [PMID: 39809453 DOI: 10.1055/a-2516-0261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
The liver is a sexually dimorphic organ. Sex differences in prevalence, progression, prognosis, and treatment prevail in most liver diseases, and the mechanism of how liver diseases act differently among male versus female patients has not been fully elucidated. Biological sex differences in normal physiology and disease arise principally from sex hormones and/or sex chromosomes. Sex hormones contribute to the development and progression of most liver diseases, with estrogen- and androgen-mediated signaling pathways mechanistically involved. In addition, genetic factors in sex chromosomes have recently been found to contribute to the sex disparity of many liver diseases, which might explain, to some extent, the difference in gene expression pattern, immune response, and xenobiotic metabolism between men and women. Although increasing evidence suggests that sex is one of the most important modulators of disease prevalence and outcomes, at present, basic and clinical studies have long been sex unbalanced, with female subjects underestimated. As such, this review focuses on sex disparities of liver diseases and summarizes the current understanding of sex-specific mechanisms, including sex hormones, sex chromosomes, etc. We anticipate that understanding sex-specific pathogenesis will aid in promoting personalized therapies for liver disease among male versus female patients.
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Affiliation(s)
- Jie-Wen Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- National-Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
| | - Nan Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- National-Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
| | - Yi Lyu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- National-Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
| | - Xu-Feng Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
- National-Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
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Cherubini A, Della Torre S, Pelusi S, Valenti L. Sexual dimorphism of metabolic dysfunction-associated steatotic liver disease. Trends Mol Med 2024; 30:1126-1136. [PMID: 38890029 DOI: 10.1016/j.molmed.2024.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 06/20/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition. MASLD is a sexually dimorphic condition, with its development and progression influenced by sex chromosomes and hormones. Estrogens typically protect against, whereas androgens promote, MASLD. Therapeutic approaches for a sex-specific personalized medicine include estrogen replacement, androgen blockers, and novel drugs targeting hormonal pathways. However, the interactions between hormonal factors and inherited genetic variation impacts MASLD risk, necessitating more tailored therapies. Understanding sex disparities and the role of estrogens could improve MASLD interventions and management, whereas clinical trials addressing sex differences are crucial for advancing personalized treatment. This review explores the underappreciated impact of sexual dimorphism in MASLD and discusses the potential therapeutic application of sex-related hormones.
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Affiliation(s)
- Alessandro Cherubini
- Department of Transfusion Medicine, Precision Medicine Lab, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Della Torre
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, 20133 Milan, Italy
| | - Serena Pelusi
- Department of Transfusion Medicine, Precision Medicine Lab, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Luca Valenti
- Department of Transfusion Medicine, Precision Medicine Lab, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
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Papadimitriou K, Mousiolis AC, Mintziori G, Tarenidou C, Polyzos SA, Goulis DG. Hypogonadism and nonalcoholic fatty liver disease. Endocrine 2024; 86:28-47. [PMID: 38771482 DOI: 10.1007/s12020-024-03878-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/12/2024] [Indexed: 05/22/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD), recently proposed to be renamed to metabolic dysfunction-associated steatotic liver disease (MASLD), is a major global public health concern, affecting approximately 25-30% of the adult population and possibly leading to cirrhosis, hepatocellular carcinoma, and liver transplantation. The liver is involved in the actions of sex steroids via their hepatic metabolism and production of the sex hormone-binding globulin (SHBG). Liver disease, including NAFLD, is associated with reproductive dysfunction in men and women, and the prevalence of NAFLD in patients with hypogonadism is considerable. A wide spectrum of possible pathophysiological mechanisms linking NAFLD and male/female hypogonadism has been investigated. As therapies targeting NAFLD may impact hypogonadism in men and women, and vice versa, treatments of the latter may affect NAFLD, and an insight into their pathophysiological pathways is imperative. This paper aims to elucidate the complex association between NAFLD and hypogonadism in men and women and discuss the therapeutic options and their impact on both conditions.
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Affiliation(s)
- Kasiani Papadimitriou
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Athanasios C Mousiolis
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Gesthimani Mintziori
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios G Goulis
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Heikelä H, Mairinoja L, Ruohonen ST, Rytkönen KT, de Brot S, Laiho A, Koskinen S, Suomi T, Elo LL, Strauss L, Poutanen M. Disruption of HSD17B12 in mouse hepatocytes leads to reduced body weight and defect in the lipid droplet expansion associated with microvesicular steatosis. FASEB J 2024; 38:e70034. [PMID: 39248019 DOI: 10.1096/fj.202400333rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 08/21/2024] [Accepted: 08/26/2024] [Indexed: 09/10/2024]
Abstract
The function of hydroxysteroid dehydrogenase 12 (HSD17B12) in lipid metabolism is poorly understood. To study this further, we created mice with hepatocyte-specific knockout of HSD17B12 (LiB12cKO). From 2 months on, these mice showed significant fat accumulation in their liver. As they aged, they also had a reduced whole-body fat percentage. Interestingly, the liver fat accumulation did not result in the typical formation of large lipid droplets (LD); instead, small droplets were more prevalent. Thus, LiB12KO liver did not show increased macrovesicular steatosis with the increasing fat content, while microvesicular steatosis was the predominant feature in the liver. This indicates a failure in the LD expansion. This was associated with liver damage, presumably due to lipotoxicity. Notably, the lipidomics data did not support an essential role of HSD17B12 in fatty acid (FA) elongation. However, we did observe a decrease in the quantity of specific lipid species that contain FAs with carbon chain lengths of 18 and 20 atoms, including oleic acid. Of these, phosphatidylcholine and phosphatidylethanolamine have been shown to play a key role in LD formation, and a limited amount of these lipids could be part of the mechanism leading to the dysfunction in LD expansion. The increase in the Cidec expression further supported the deficiency in LD expansion in the LiB12cKO liver. This protein is crucial for the fusion and growth of LDs, along with the downregulation of several members of the major urinary protein family of proteins, which have recently been shown to be altered during endoplasmic reticulum stress.
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Affiliation(s)
- Hanna Heikelä
- Research Centre for Integrative Physiology and Pharmacology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Laura Mairinoja
- Research Centre for Integrative Physiology and Pharmacology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Suvi T Ruohonen
- Research Centre for Integrative Physiology and Pharmacology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Kalle T Rytkönen
- Research Centre for Integrative Physiology and Pharmacology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
| | - Simone de Brot
- COMPATH, Institute of Animal Pathology, University of Bern, Bern, Switzerland
| | - Asta Laiho
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
| | - Satu Koskinen
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
| | - Tomi Suomi
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
| | - Laura L Elo
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
| | - Leena Strauss
- Research Centre for Integrative Physiology and Pharmacology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Matti Poutanen
- Research Centre for Integrative Physiology and Pharmacology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland
- Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Polyzos SA, Goulis DG. Menopause and metabolic dysfunction-associated steatotic liver disease. Maturitas 2024; 186:108024. [PMID: 38760254 DOI: 10.1016/j.maturitas.2024.108024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 05/02/2024] [Accepted: 05/04/2024] [Indexed: 05/19/2024]
Abstract
Nonalcoholic fatty liver disease, recently proposed to be renamed metabolic dysfunction-associated steatotic liver disease, is a highly prevalent disease (25-30 % of the global general population) whose prevalence increases after menopause. Apart from the rates of simple steatosis, the severity of the disease (e.g., hepatic fibrosis) increases after menopause. Menopause is associated with higher abdominal adiposity and dysmetabolism of carbohydrate and lipid metabolism, which may contribute to the development and severity of metabolic dysfunction-associated steatotic liver disease and the higher cardiovascular risk observed after menopause. The association between menopause and metabolic dysfunction-associated steatotic liver disease renders menopausal hormone therapy an appealing way to reverse hepatic disease in parallel with the benefits of menopausal hormone therapy in other tissues. In this regard, most animal studies have shown a beneficial effect of estrogens on metabolic dysfunction-associated steatotic liver disease. Still, clinical studies are few, and their data are conflicting. The effect of menopausal hormone therapy on metabolic dysfunction-associated steatotic liver disease may be distinct among estrogen monotherapies and the combinations of estrogens and progestogens. It may also depend on the type of progestogen and the route of administration. However, more studies specifically designed for these aims are needed to draw secure conclusions. This review summarizes the data related to the association between menopause and metabolic dysfunction-associated steatotic liver disease, as well as between menopausal hormone therapy and metabolic dysfunction-associated steatotic liver disease, with a special focus on clinical studies.
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Affiliation(s)
- Stergios A Polyzos
- First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Campus of Aristotle University, 54124 Thessaloniki, Greece.
| | - Dimitrios G Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Ring Road, 56403 Thessaloniki, Greece.
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Mintziori G, Veneti S, Poppe K, Goulis DG, Armeni E, Erel CT, Fistonić I, Hillard T, Hirschberg AL, Meczekalski B, Mendoza N, Mueck AO, Simoncini T, Stute P, van Dijken D, Rees M, Duntas L, Lambrinoudaki I. EMAS position statement: Thyroid disease and menopause. Maturitas 2024; 185:107991. [PMID: 38658290 DOI: 10.1016/j.maturitas.2024.107991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
INTRODUCTION Thyroid diseases are common in women in their late reproductive years; therefore, thyroid disease and menopause may co-exist. Both conditions may present with a wide range of symptoms, leading to diagnostic challenges and delayed diagnosis. Aim To construct the first European Menopause and Andropause Society (EMAS) statement on thyroid diseases and menopause. MATERIALS AND METHODS Literature review and consensus of expert opinion (EMAS executive board members/experts on menopause and thyroid disease). SUMMARY RECOMMENDATIONS This position paper highlights the diagnostic and therapeutic dilemmas in managing women with thyroid disease during the menopausal transition, aiming to increase healthcare professionals' awareness of thyroid disorders and menopause-related symptoms. Clinical decisions regarding the treatment of both conditions should be made with caution and attention to the specific characteristics of this age group while adopting a personalized patient approach. The latter must include the family history, involvement of the woman in the decision-making, and respect for her preferences, to achieve overall well-being.
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Affiliation(s)
- Gesthimani Mintziori
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece.
| | - Stavroula Veneti
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece
| | - Kris Poppe
- University Hospital CHU St-Pierre UMC, Université libre de Bruxelles (ULB), Belgium
| | - Dimitrios G Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece
| | - Eleni Armeni
- Second Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Greece and Royal Free Hospital, London, United Kingdom
| | - C Tamer Erel
- Istanbul-Cerrahpaşa University, Cerrahpaşa School of Medicine, Department of Obstetrics and Gynecology, İstanbul, Turkey
| | - Ivan Fistonić
- Faculty for Health Studies, University of Rijeka, Rijeka, Croatia
| | - Timothy Hillard
- Department of Obstetrics and Gynaecology, University Hospitals Dorset, Poole, UK
| | - Angelica Lindén Hirschberg
- Department of Women's and Children's Health, Karolinska Institutet and Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Blazej Meczekalski
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland
| | - Nicolás Mendoza
- Department of Obstetrics and Gynecology, University of Granada, Spain
| | - Alfred O Mueck
- Department of Women's Health, University Hospital Tuebingen, Germany; Beijing OB/GYN Hospital, Capital Medical University, China
| | - Tommaso Simoncini
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy
| | - Petra Stute
- Department of Obstetrics and Gynecology, University Clinic Inselspital, Bern, Switzerland
| | - Dorenda van Dijken
- Department of Obstetrics and Gynecology, OLVG Hospital, Amsterdam, The Netherlands
| | - Margaret Rees
- Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK
| | - Leonidas Duntas
- Evgenideion Hospital, Unit of Endocrinology and Metabolism, National and Kapodistrian University, Athens, Greece
| | - Irene Lambrinoudaki
- Second Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Greece
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Bulatova IA, Shevlyukova TP. Features of the course of non-alcoholic fatty liver disease in women at different age periods: literature review. MEDITSINSKIY SOVET = MEDICAL COUNCIL 2024:90-95. [DOI: 10.21518/ms2024-112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
The review examines the epidemiology and risk factors of non-alcoholic fatty liver disease (NAFLD) for women. According to various sources, the global prevalence of NAFLD ranges from 20 to 40% of the adult population in the world. In Russia, 37.3% of polyclinic patients have NAFLD. NAFLD can occur at any age and has differences in prevalence and severity depending on ethnicity and gender. Over the past 10 years, there has been a trend towards an increase in the prevalence of NAFLD among women, as well as a sharper increase in mortality compared to men. Regardless of gender, prognostically significant risk factors for NAFLD include age, obesity, type 2 diabetes mellitus, insulin resistance, dyslipidemia. The clinical course and prognosis of NAFLD in women depends on age, reproductive stage and use of synthetic hormones. Premenopausal women have less pronounced liver fibrosis and a better life prognosis compared to postmenopausal men and women. The article describes the features of the course of NAFLD in the reproductive period, pre- and postmenopausal period, characterizes the effect of liver steatosis on the course and outcome of pregnancy, the perinatal condition of the mother and fetus. Thus, there are gender differences in the prevalence, risk factors, fibrosis, and clinical outcomes of NAFLD. The prevalence and severity of NAFLD in reproductive age is higher in men, but after menopause, there is an increase in this pathology in women, especially those with metabolic disorders. Liver steatosis can affect the course of pregnancy, labor and postpartum periods.
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Ntikoudi A, Spyrou A, Evangelou E, Dokoutsidou E, Mastorakos G. The Effect of Menopausal Status, Insulin Resistance and Body Mass Index on the Prevalence of Non-Alcoholic Fatty Liver Disease. Healthcare (Basel) 2024; 12:1081. [PMID: 38891156 PMCID: PMC11171981 DOI: 10.3390/healthcare12111081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 05/04/2024] [Accepted: 05/09/2024] [Indexed: 06/21/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is common and presents in a large proportion-up to 30%-of the global adult female population. Several factors have been linked with NAFLD in women, such as age, obesity, and metabolic syndrome. To extract appropriate details about the topic, we conducted an extensive search using various medical subject headings and entry terms including 'Menopause', 'Non-alcoholic fatty liver disease', 'Insulin resistance', and 'BMI'. This exhaustive search resulted in a total of 180 studies, among which only 19 were able to meet the inclusion criteria. While most of these studies indicated a significant rise in NAFLD prevalence among postmenopausal women, two did not find strong evidence linking menopause with NAFLD. Moreover, it was observed that women with NAFLD had higher insulin resistance levels and BMIs compared to those without the condition. In summary, it is important to consider specific factors like risk profile, hormonal status, and age along with metabolic components when treating women presenting with NAFLD. There is need for data-driven research on how gender affects the sensitivity of biomarkers towards NAFLD as well as the development of sex-specific prediction models-this would help personalize management approaches for women, who stand to benefit greatly from such tailored interventions.
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Affiliation(s)
- Anastasia Ntikoudi
- Department of Nursing, University of West Attica, 12243 Athens, Greece; (A.S.); (E.E.); (E.D.)
| | - Alketa Spyrou
- Department of Nursing, University of West Attica, 12243 Athens, Greece; (A.S.); (E.E.); (E.D.)
| | - Eleni Evangelou
- Department of Nursing, University of West Attica, 12243 Athens, Greece; (A.S.); (E.E.); (E.D.)
| | - Eleni Dokoutsidou
- Department of Nursing, University of West Attica, 12243 Athens, Greece; (A.S.); (E.E.); (E.D.)
| | - George Mastorakos
- Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieion University Hospital, Medical School of Athens, Ethnikon and Kapodistriakon University of Athens, 11528 Athens, Greece;
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Jin Z, Tian C, Kang M, Hu S, Zhao L, Zhang W. The 100 top-cited articles in menopausal syndrome: a bibliometric analysis. Reprod Health 2024; 21:47. [PMID: 38589898 PMCID: PMC11003046 DOI: 10.1186/s12978-024-01770-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Accepted: 03/10/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Significant scientific research has been conducted concerning menopausal syndrome(MPS), yet few bibliometric analyses have been performed. Our aim was to recognise the 100 most highly cited published articles on MPS and to analytically evaluate their key features. METHODS To identify the 100 most frequently cited articles, a search was conducted on Web of Science using the term 'menopausal syndrome'. Articles that matched the predetermined criteria were scrutinised to obtain the following data: citation ranking, year of publication, publishing journal, journal impact factor, country of origin, academic institution, authors, study type, and keywords. RESULTS The publication period is from January 1, 2000, to August 31, 2022. The maximum number of citations was 406 and in 2012. The median citations per year was 39.70. Most of the articles focused on treatment and complications. These articles were published in 36 different journals, with the Journal of MENOPAUSE having published the greatest number (14%). Forty-eight articles (48%) were from the United States, with the University of Pittsburgh being the leading institute (9%). Joann E. Manson was the most frequent first author (n = 6). Observational studies were the most frequently conducted research type (n = 53), followed by experimental studies (n = 33). Keyword analysis identified classic research topics, including genitourinary syndrome of menopause, bone mineral density (BMD), and anti-mullerian hormone (AMH) loci. CONCLUSION Using bibliometrics, we conducted an analysis to identify the inadequacies, traditional focal points, and potential prospects in the study of MPS across current scientific areas. Treatment and complications are at the core of MPS research, whereas prediction and biomarkers have less literature of high quality. There is a necessity for innovative analytical metrics to measure the real effect of these papers with a high level of citation on clinical application.
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Affiliation(s)
- Zishan Jin
- Beijing University of Chinese Medicine, Beijing, 100029, China
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Chuanxi Tian
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Mengjiao Kang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Shiwan Hu
- Beijing University of Chinese Medicine, Beijing, 100029, China
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Linhua Zhao
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
| | - Wei Zhang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
- Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China.
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11
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Cherubini A, Casirati E, Pelusi S, Valenti L. Estrogen-ER-α axis induces PNPLA3 p.I148M protein variant to promote steatotic liver disease susceptibility in women. Clin Transl Med 2024; 14:e1524. [PMID: 38224202 PMCID: PMC10788875 DOI: 10.1002/ctm2.1524] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 12/12/2023] [Indexed: 01/16/2024] Open
Affiliation(s)
- Alessandro Cherubini
- Department of Transfusion MedicinePrecision Medicine Lab, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Elia Casirati
- Department of Pathophysiology and TransplantationUniversità Degli Studi di MilanoMilanItaly
| | - Serena Pelusi
- Department of Transfusion MedicinePrecision Medicine Lab, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Luca Valenti
- Department of Transfusion MedicinePrecision Medicine Lab, Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
- Department of Pathophysiology and TransplantationUniversità Degli Studi di MilanoMilanItaly
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Ferenc K, Jarmakiewicz-Czaja S, Filip R. What Does Sarcopenia Have to Do with Nonalcoholic Fatty Liver Disease? Life (Basel) 2023; 14:37. [PMID: 38255652 PMCID: PMC10820621 DOI: 10.3390/life14010037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/11/2023] [Accepted: 12/16/2023] [Indexed: 01/24/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. As the second stage of developing steatosis, nonalcoholic hepatitis (NASH) carries the risk of fibrosis, cirrhosis, and hepatocellular carcinoma. Sarcopenia is defined as a condition characterized by a decrease in muscle mass and functional decline. Both NAFLD and sarcopenia are global problems. The pathophysiological mechanisms that link the two entities of the disease are insulin resistance, inflammation, nutritional deficiencies, impairment of myostatin and adiponectin, or physical inactivity. Furthermore, disorders of the gut-liver axis appear to induce the process of developing NAFLD and sarcopenia. The correlations between NAFLD and sarcopenia appear to be bidirectional, so the main objective of the review was to determine the cause-and-effect relationship between the two diseases.
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Affiliation(s)
- Katarzyna Ferenc
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland;
| | | | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland;
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
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13
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Malucelli M, Strobel R, Ivantes C, Sakamoto D, Luís Duarte M, Lucia Alves Pedroso M. Histological findings and NAFLD/NASH Status in liver biopsies of patients subjected to bariatric surgery. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2023; 68:e220138. [PMID: 37948562 PMCID: PMC10916797 DOI: 10.20945/2359-4292-2022-0138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 04/11/2023] [Indexed: 11/12/2023]
Abstract
Objective To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1.
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Affiliation(s)
- Marielle Malucelli
- Departamento de Pós-graduação em Medicina Interna, Universidade Federal do Paraná, Curitiba, PR, Brasil,
| | - Rodrigo Strobel
- Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brasil
| | | | | | - Márcio Luís Duarte
- Departamento de Radiologia, Universidade de Ribeirão Preto Campus Guarujá, Guarujá, SP, Brasil
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14
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Takahashi A, Takahata Y, Kokubun M, Anzai Y, Kogure A, Ogata T, Abe N, Sugaya T, Fujita M, Imaizumi H, Hayashi M, Abe K, Ohira H. Association between equol and non-alcoholic fatty liver disease in Japanese women in their 50s and 60s. J Gastroenterol Hepatol 2023; 38:1958-1962. [PMID: 37565591 DOI: 10.1111/jgh.16315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 07/13/2023] [Accepted: 07/22/2023] [Indexed: 08/12/2023]
Abstract
BACKGROUND AND AIM Equol is a metabolite of soy isoflavone and has estrogenic activity. The incidence of non-alcoholic fatty liver disease (NAFLD) increases after menopause in women, which is thought to result in a decrease in estrogen. This study aimed to evaluate the association between equol and NAFLD. METHODS We evaluated 1185 women aged 50-69 years who underwent health check-ups at four health centers in Fukushima, Japan. Equol producers were defined by a urinary equol concentration of 1.0 μM or more. In addition to comparison between equol producers and non-producers, the association between equol and NAFLD was estimated using logistic regression analysis adjusting for fast walking and eating habits. RESULTS Of the 1185 participants, 345 (29.1%) women were equol producers. The proportions of women who had NAFLD (34.8% vs 45.2%) were significantly lower in the equol-producing group than in the non-producing group. Multivariable logistic regression analysis showed that equol production was significantly associated with NAFLD (odds ratio = 0.66, 95% confidence interval: 0.51-0.86). CONCLUSIONS Equol production was significantly associated with NAFLD in women in their 50s and 60s.
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Affiliation(s)
- Atsushi Takahashi
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Yosuke Takahata
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Masae Kokubun
- Institution for Total Medical Checkup, Jusendo Clinic, Fukushima, Japan
| | - Yukio Anzai
- Department of Gastroenterology, Watari Hospital, Fukushima, Japan
| | - Atsuko Kogure
- Department of Gastroenterology, Fujita General Hospital, Fukushima, Japan
| | - Takashi Ogata
- Department of Gastroenterology, Masu Memorial Hospital, Fukushima, Japan
| | - Naoto Abe
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Tatsuro Sugaya
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Masashi Fujita
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Hiromichi Imaizumi
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Manabu Hayashi
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University, School of Medicine, Fukushima, Japan
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15
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Wang M, Li S, Zhang X, Li X, Cui J. Association between hemoglobin glycation index and non-alcoholic fatty liver disease in the patients with type 2 diabetes mellitus. J Diabetes Investig 2023; 14:1303-1311. [PMID: 37551797 PMCID: PMC10583654 DOI: 10.1111/jdi.14066] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 07/20/2023] [Accepted: 07/24/2023] [Indexed: 08/09/2023] Open
Abstract
AIMS/INTRODUCTION The hemoglobin glycation index (HGI) represent the disparity between actual glycated hemoglobin measurements and predicted HbA1c. It serves as a proxy for the degree of non-enzymatic glycation of hemoglobin, which has been found to be positively correlated with diabetic comorbidities. In this study, we investigated the relationship between HGI and non-alcoholic fatty liver disease (NAFLD), along with other relevant biological markers in patients with diabetes. MATERIALS AND METHODS This cross-sectional study consisted of 3,191 adults diagnosed with type 2 diabetes mellitus. We calculated the predicted glycated hemoglobin levels based on fasting blood glucose levels. Multivariate binary logistic regression analysis was conducted to examine the correlation between the HGI and NAFLD. Hepatic steatosis was diagnosed using ultrasonography. RESULTS Among all participants, 1,784 (55.91%) were diagnosed with NAFLD. Participants with confirmed NAFLD showed elevated body mass index, diastolic blood pressure, liver enzyme, total cholesterol, triglyceride, low-density lipoprotein and uric acid levels compared with those without NAFLD. In the unadjusted model, participants in the last tertile of HGI were 1.40-fold more likely to develop NAFLD than those in the first tertile (95% confidence interval 1.18-1.66; P < 0.001). In the fully adjusted model, those in the last tertile of HGI had a 39% increased risk of liver steatosis compared with confidence interval in the first tertile of HGI (95% confidence interval 1.12-1.74; P < 0.001). CONCLUSIONS A higher HGI suggests an elevated risk of developing NAFLD in patients with type 2 diabetes.
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Affiliation(s)
- Meng Wang
- Department of Endocrinology and MetabolismTianjin Medical University General HospitalTianjinChina
| | - Shiwei Li
- Department of Endocrinology and MetabolismTianjin Medical University General HospitalTianjinChina
| | - Xinxin Zhang
- Department of Endocrinology and MetabolismTianjin Medical University General HospitalTianjinChina
| | - Xin Li
- Department of Endocrinology and MetabolismTianjin Medical University General HospitalTianjinChina
| | - Jingqiu Cui
- Department of Endocrinology and MetabolismTianjin Medical University General HospitalTianjinChina
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Danpanichkul P, Kongarin S, Permpatdechakul S, Polpichai N, Duangsonk K, Manosroi W, Chaiyakunapruk N, Mousa OY, Kim D, Chen VL, Wijarnpreecha K. The Surreptitious Burden of Nonalcoholic Fatty Liver Disease in the Elderly in the Asia-Pacific Region: An Insight from the Global Burden of Disease Study 2019. J Clin Med 2023; 12:6456. [PMID: 37892594 PMCID: PMC10607093 DOI: 10.3390/jcm12206456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 09/28/2023] [Accepted: 10/08/2023] [Indexed: 10/29/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The aging population and a rise in metabolic syndrome in Asia might influence the epidemiology of NAFLD among the elderly. However, there is a lack of understanding of the burden and recommendations for NAFLD in this group. Our study sought to investigate the trends in the NAFLD burden among the elderly in the Asia-Pacific region. We employed data from the Global Burden of Disease 2019 study for an in-depth analysis of the prevalence and disability-adjusted life years (DALYs) along with age-standardized rate (ASR) associated with NAFLD in elderly populations (age 65-89 years) across the Asia-Pacific region, including the Southeast Asia (SEA) and Western Pacific (WP) regions, from 2010 to 2019. This study also examined the trends and disparities in NAFLD burden across different nations and sexes. In 2019, there were over 120 million cases of NAFLD in the elderly in the Asia-Pacific region. The ASR of prevalence was higher in SEA compared to WP (36,995.37 vs. 32,821.78 per 100,000). ASR of prevalence increased with annual percentage change (APC) +0.95% in the WP while it increased by +0.87% in SEA. During the study period, the ASR of DALYs decreased in SEA (APC -0.41%) but remained stable in the WP region. The burden of NAFLD in the elderly population in Asia-Pacific has increased, underscoring the timely intervention to tackle this high and rising burden.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Siwanart Kongarin
- Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | | | - Natchaya Polpichai
- Department of Internal Medicine, Weiss Memorial Hospital, Chicago, IL 60640, USA;
| | - Kwanjit Duangsonk
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Worapaka Manosroi
- Division of Endocrinology, Department of Internal Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Clinical Epidemiology and Clinical Statistics Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Nathorn Chaiyakunapruk
- Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA;
- IDEAS Center, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT 84108, USA
| | - Omar Y. Mousa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Mayo Clinic Health System, Rochester, MN 55902, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA;
| | - Vincent L. Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 41809, USA
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner University Medical Center, Phoenix, AZ 85006, USA
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17
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Eng PC, Forlano R, Tan T, Manousou P, Dhillo WS, Izzi-Engbeaya C. Non-alcoholic fatty liver disease in women - Current knowledge and emerging concepts. JHEP Rep 2023; 5:100835. [PMID: 37771547 PMCID: PMC10522907 DOI: 10.1016/j.jhepr.2023.100835] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 05/26/2023] [Accepted: 06/05/2023] [Indexed: 09/30/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide, affecting up to 30% of adults. Progression to non-alcoholic steatohepatitis (NASH) is a key risk factor for cirrhosis, hepatocellular carcinoma and cardiovascular events. Alterations in reproductive hormones are linked to the development and/or progression of NAFLD/NASH in women. Women with polycystic ovary syndrome and those with oestrogen deficiency are at increased risk of NAFLD/NASH, with higher mortality rates in older women compared to men of similar ages. NAFLD/NASH is currently the leading indication for liver transplantation in women without hepatocellular carcinoma. Therefore, a better understanding of NAFLD in women is needed to improve outcomes. In this review, we discuss the hormonal and non-hormonal factors that contribute to NAFLD development and progression in women. Furthermore, we highlight areas of focus for clinical practice and for future research.
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Affiliation(s)
- Pei Chia Eng
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Diabetes and Endocrinology, Imperial College Healthcare NHS Trust, London, UK
| | - Roberta Forlano
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Hepatology, Imperial College Healthcare NHS Trust, London, UK
| | - Tricia Tan
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Diabetes and Endocrinology, Imperial College Healthcare NHS Trust, London, UK
| | - Pinelopi Manousou
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Hepatology, Imperial College Healthcare NHS Trust, London, UK
| | - Waljit S. Dhillo
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Diabetes and Endocrinology, Imperial College Healthcare NHS Trust, London, UK
| | - Chioma Izzi-Engbeaya
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Diabetes and Endocrinology, Imperial College Healthcare NHS Trust, London, UK
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18
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Kim SE, Min JS, Lee S, Lee DY, Choi D. Different effects of menopausal hormone therapy on non-alcoholic fatty liver disease based on the route of estrogen administration. Sci Rep 2023; 13:15461. [PMID: 37726372 PMCID: PMC10509271 DOI: 10.1038/s41598-023-42788-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 09/14/2023] [Indexed: 09/21/2023] Open
Abstract
The effects of menopausal hormone therapy (MHT) on non-alcoholic fatty liver disease (NAFLD) were compared based on the route of estrogen administration. The study included 368 postmenopausal women who received MHT for 12 months. Patients were divided into transdermal (n = 75) and oral (n = 293) groups based on the estrogen route. Changes in the prevalence of NAFLD were compared between the two groups before and after 12 months of MHT. In addition, differences in the progression of NAFLD after MHT based on the dose of estrogen and type of progestogen were evaluated in the oral group. After MHT, the prevalence of NAFLD decreased from 24 to 17.3% in the transdermal group but increased from 25.3 to 29.4% in the oral group. Little or no change was found in clinical characteristics and laboratory tests in the transdermal group during MHT. However, serum levels of total cholesterol and low-density lipoprotein cholesterol decreased and triglycerides and high-density lipoprotein cholesterol increased significantly in the oral group. Furthermore, changes in the prevalence of NAFLD were not significantly different based on the dose of estrogen or type of progestogen. Our findings indicate that transdermal estrogen can be beneficial in terms of NAFLD progression.
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Affiliation(s)
- Sung Eun Kim
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Ji-Song Min
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Saemi Lee
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
| | - Dong-Yun Lee
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.
| | - DooSeok Choi
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea
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19
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Hieber C, Grabbe S, Bros M. Counteracting Immunosenescence-Which Therapeutic Strategies Are Promising? Biomolecules 2023; 13:1085. [PMID: 37509121 PMCID: PMC10377144 DOI: 10.3390/biom13071085] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 07/03/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023] Open
Abstract
Aging attenuates the overall responsiveness of the immune system to eradicate pathogens. The increased production of pro-inflammatory cytokines by innate immune cells under basal conditions, termed inflammaging, contributes to impaired innate immune responsiveness towards pathogen-mediated stimulation and limits antigen-presenting activity. Adaptive immune responses are attenuated as well due to lowered numbers of naïve lymphocytes and their impaired responsiveness towards antigen-specific stimulation. Additionally, the numbers of immunoregulatory cell types, comprising regulatory T cells and myeloid-derived suppressor cells, that inhibit the activity of innate and adaptive immune cells are elevated. This review aims to summarize our knowledge on the cellular and molecular causes of immunosenescence while also taking into account senescence effects that constitute immune evasion mechanisms in the case of chronic viral infections and cancer. For tumor therapy numerous nanoformulated drugs have been developed to overcome poor solubility of compounds and to enable cell-directed delivery in order to restore immune functions, e.g., by addressing dysregulated signaling pathways. Further, nanovaccines which efficiently address antigen-presenting cells to mount sustained anti-tumor immune responses have been clinically evaluated. Further, senolytics that selectively deplete senescent cells are being tested in a number of clinical trials. Here we discuss the potential use of such drugs to improve anti-aging therapy.
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Affiliation(s)
- Christoph Hieber
- Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany
| | - Stephan Grabbe
- Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany
| | - Matthias Bros
- Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
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20
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Li M, Zhang W, Li X, Liang S, Zhang Y, Mo Y, Rao S, Zhang H, Huang Y, Zhu Y, Zhang Z, Yang W. Metabolic and Risk Profiles of Lean and Non-Lean Hepatic Steatosis among US Adults. Nutrients 2023; 15:2856. [PMID: 37447183 DOI: 10.3390/nu15132856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
Hepatic steatosis can occur in lean individuals, while its metabolic and risk profiles remain unclear. We aimed to characterize the clinical and risk profiles of lean and non-lean steatosis. This cross-sectional study included 1610 patients with transient elastography-assessed steatosis. The metabolic and risk profiles were compared. Compared to their non-lean counterparts, lean subjects with steatosis had a lower degree of fibrosis (F0-F1: 91.9% vs. 80.9%), had a lower prevalence of diabetes (27.9% vs. 32.8%), dyslipidemia (54.7% vs. 60.2%) and hypertension (50.0% vs. 51.3%), and had higher levels of high-density lipoprotein cholesterol while lower fasting insulin and homeostatic model assessment for insulin resistance (all p < 0.05). Of the 16 potential risk factors, being Hispanic was associated with higher odds of non-lean steatosis but not with lean steatosis (odds ratio (OR): 2.07 vs. 0.93), while excessive alcohol consumption had a different trend in the ratio (OR: 1.47 vs.6.65). Higher waist-to-hip ratio (OR: 7.48 vs. 2.45), and higher waist circumference (OR: 1.14 vs. 1.07) showed a stronger positive association with lean steatosis than with non-lean steatosis (all Pheterogeneity < 0.05). Although lean individuals with steatosis presented a healthier metabolic profile, both lean and non-lean steatosis had a significant proportion of metabolic derangements. In addition, the etiological heterogeneity between lean and non-lean steatosis may exist.
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Affiliation(s)
- Meiling Li
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
- Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei 230032, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics/Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei 230032, China
| | - Weiping Zhang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Xiude Li
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Shaoxian Liang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Yaozong Zhang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Yufeng Mo
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Songxian Rao
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Honghua Zhang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Yong Huang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Yu Zhu
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Zhuang Zhang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
| | - Wanshui Yang
- Department of Nutrition, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, China
- Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei 230032, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics/Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei 230032, China
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21
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Rashad Mostafa N, Ali AA, Alkaphoury MG, Marzo RR. <i>Helicobacter Pylori</i> infection and non-alcoholic fatty liver disease. Is there a relationship? HEALTHCARE IN LOW-RESOURCE SETTINGS 2023; 11. [DOI: 10.4081/hls.2023.11379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The most prevalent infection that causes chronic gastritis, gastric ulcers, and gastric cancer is Helicobacter pylori infection. Recent research has implicated H. pylori in the pathogenesis of non-gastrointestinal diseases such as cardiovascular, autoimmune, and metabolic disorders. In addition, since H. pylori is believed to be implicated in insulin resistance, numerous studies have been conducted to determine the relationship between H. pylori infection and nonalcoholic fatty liver diseases (NAFLD), but the results have been contested. The purpose of this study is to determine the relationship between H. Pylori infection and nonalcoholic fatty liver diseases. One hundred patients were examined via urea breath test for the presence of H. pylori infection and vibration-controlled transient elastography for the diagnosis of non-alcoholic fatty liver disease. After adjusting for other variables, age, body mass index (BMI), and H. pylori infection were associated with elastography 248dB/m. Infection with H. pylori contributes to the development of NAFLD, and its eradication may influence prognosis.
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22
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DiStefano JK. The Role of Choline, Soy Isoflavones, and Probiotics as Adjuvant Treatments in the Prevention and Management of NAFLD in Postmenopausal Women. Nutrients 2023; 15:2670. [PMID: 37375574 DOI: 10.3390/nu15122670] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/05/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition among postmenopausal women that can lead to severe liver dysfunction and increased mortality. In recent years, research has focused on identifying potential lifestyle dietary interventions that may prevent or treat NAFLD in this population. Due to the complex and multifactorial nature of NAFLD in postmenopausal women, the disease can present as different subtypes, with varying levels of clinical presentation and variable treatment responses. By recognizing the significant heterogeneity of NAFLD in postmenopausal women, it may be possible to identify specific subsets of individuals who may benefit from targeted nutritional interventions. The purpose of this review was to examine the current evidence supporting the role of three specific nutritional factors-choline, soy isoflavones, and probiotics-as potential nutritional adjuvants in the prevention and treatment of NAFLD in postmenopausal women. There is promising evidence supporting the potential benefits of these nutritional factors for NAFLD prevention and treatment, particularly in postmenopausal women, and further research is warranted to confirm their effectiveness in alleviating hepatic steatosis in this population.
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Affiliation(s)
- Johanna K DiStefano
- Diabetes and Metabolic Disease Research Unit, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
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Jaroenlapnopparat A, Charoenngam N, Ponvilawan B, Mariano M, Thongpiya J, Yingchoncharoen P. Menopause is associated with increased prevalence of nonalcoholic fatty liver disease: a systematic review and meta-analysis. Menopause 2023; 30:348-354. [PMID: 36728528 DOI: 10.1097/gme.0000000000002133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
IMPORTANCE Data are inconsistent on whether menopause is a risk for nonalcoholic fatty liver disease (NAFLD). OBJECTIVE Using systematic review and meta-analysis, we aimed to collect all available data to determine the association between menopause and NAFLD. EVIDENCE REVIEW Potentially eligible studies were identified from EMBASE, MEDLINE, and Web of Science databases from inception to December 2021 using a search strategy that was composed of the terms for "NAFLD" and "menopause." Eligible study must contain two groups of participants: one group of postmenopausal women and another group of premenopausal women. Then, the study must report the association between menopause and prevalent NAFLD. We extracted such data from each study and calculated pooled odds ratio (OR) by combining effect estimates of each study using a random-effects model. Funnel plot was used to assess for the presence of publication bias. FINDINGS A total of 587 articles were identified. After two rounds of independent review by two investigators, 12 cross-sectional studies fulfilled the eligibility criteria. The meta-analysis of 12 studies revealed the significant association between menopause and NAFLD with a pooled OR of 2.37 (95% CI, 1.99-2.82; I2 = 73%). The association remained significant in a sensitivity meta-analysis of six studies that reported the association with adjustment for age and metabolic factors with a pooled OR of 2.19 (95% CI, 1.73-2.78; I2 = 74%). The funnel plot was fairly symmetric and was not suggestive of publication bias. CONCLUSIONS AND RELEVANCE The meta-analysis reveals that menopausal status was associated with approximately 2.4 times higher odds of NAFLD.
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Affiliation(s)
| | | | - Ben Ponvilawan
- Department of Medicine, University of Missouri-Kansas City School of Medicine, Kansas City, MO
| | | | - Jerapas Thongpiya
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX
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Krznarić J, Vince A. The Role of Non-Alcoholic Fatty Liver Disease in Infections. LIFE (BASEL, SWITZERLAND) 2022; 12:life12122052. [PMID: 36556417 PMCID: PMC9788238 DOI: 10.3390/life12122052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 11/30/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, affecting one third of the Western population. The hallmark of the disease is excessive storage of fat in the liver. Most commonly, it is caused by metabolic syndrome (or one of its components). Even though the development of NAFLD has multiple effects on the human organism resulting in systemic chronic low-grade inflammation, this review is focused on NAFLD as a risk factor for the onset, progression, and outcomes of infectious diseases. The correlation between NAFLD and infections is still unclear. Multiple factors (obesity, chronic inflammation, altered immune system function, insulin resistance, altered intestinal microbiota, etc.) have been proposed to play a role in the development and progression of infections in people with NAFLD, although the exact mechanism and the interplay of mentioned factors is still mostly hypothesized. In this article we review only the selection of well-researched topics on NAFLD and infectious diseases (bacterial pneumonia, COVID, H. pylori, urinary tract infections, C. difficile, bacteremia, hepatitis B, hepatitis C, HIV, and periodontitis).
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Affiliation(s)
- Juraj Krznarić
- Department for Infectious Diseases, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Department for Viral Hepatitis, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia
| | - Adriana Vince
- Department for Infectious Diseases, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Department for Viral Hepatitis, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia
- Correspondence:
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25
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Fuller KNZ, McCoin CS, Stierwalt H, Allen J, Gandhi S, Perry CGR, Jambal P, Shankar K, Thyfault JP. Oral combined contraceptives induce liver mitochondrial reactive oxygen species and whole-body metabolic adaptations in female mice. J Physiol 2022; 600:5215-5245. [PMID: 36326014 DOI: 10.1113/jp283733] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 10/17/2022] [Indexed: 11/06/2022] Open
Abstract
Compared to age-matched men, pre-menopausal women show greater resilience against cardiovascular disease (CVD), hepatic steatosis, diabetes and obesity - findings that are widely attributed to oestrogen. However, meta-analysis data suggest that current use of oral combined contraceptives (OC) is a risk factor for myocardial infarction, and OC use further compounds with metabolic disease risk factors to increase CVD susceptibility. While mitochondrial function in tissues such as the liver and skeletal muscle is an emerging mechanism by which oestrogen may confer its protection, effects of OC use on mitochondria and metabolism in the context of disease risk remain unexplored. To answer this question, female C57Bl/6J mice were fed a high fat diet and treated with vehicle or OCs for 3, 12 or 20 weeks (n = 6 to 12 per group) at a dose and ratio that mimic the human condition of cycle cessation in the low oestrogen, high progesterone stage. Liver and skeletal muscle mitochondrial function (respiratory capacity, H2 O2 , coupling) was measured along with clinical outcomes of cardiometabolic disease such as obesity, glucose tolerance, hepatic steatosis and aortic atherosclerosis. The main findings indicate that regardless of treatment duration, OCs robustly increase hepatic mitochondrial H2 O2 levels, likely due to diminished antioxidant capacity, but have no impact on muscle mitochondrial H2 O2 . Furthermore, OC-treated mice had lower adiposity and hepatic triglyceride content compared to control mice despite reduced wheel running, spontaneous physical activity and total energy expenditure. Together, these studies describe tissue-specific effects of OC use on mitochondria as well as variable impacts on markers of metabolic disease susceptibility. KEY POINTS: Oestrogen loss in women increases risk for cardiometabolic diseases, a link that has been partially attributed to negative impacts on mitochondria and energy metabolism. To study the effect of oral combined contraceptives (OCs) on hepatic and skeletal muscle mitochondria and whole-body energy metabolism, we used an animal model of OCs which mimics the human condition of cessation of hormonal cycling in the low oestrogen, high progesterone state. OC-treated mice have increased hepatic mitochondrial oxidative stress and decreased physical activity and energy expenditure, despite displaying lower adiposity and liver fat at this time point. These pre-clinical data reveal tissue-specific effects of OCs that likely underlie the clinical findings of increased cardiometabolic disease in women who use OCs compared to non-users, when matched for obesity.
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Affiliation(s)
- Kelly N Z Fuller
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.,Research Service, Kansas City Veterans Affairs Medical Center, Kansas City, MO, USA
| | - Colin S McCoin
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.,Research Service, Kansas City Veterans Affairs Medical Center, Kansas City, MO, USA.,Center for Children's Healthy Lifestyles and Nutrition, Kansas City, MO, USA.,University of Kansas Diabetes Institute, Kansas City, KS, USA.,Kansas Center for Metabolism and Obesity Research, Kansas City, KS, USA
| | - Harrison Stierwalt
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.,Research Service, Kansas City Veterans Affairs Medical Center, Kansas City, MO, USA
| | - Julie Allen
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.,Research Service, Kansas City Veterans Affairs Medical Center, Kansas City, MO, USA
| | - Shivam Gandhi
- School of Kinesiology and Health Science, Muscle Health Research Center, York University, Toronto, Canada
| | - Christopher G R Perry
- School of Kinesiology and Health Science, Muscle Health Research Center, York University, Toronto, Canada
| | - Purevsuren Jambal
- Department of Pediatrics, Section of Nutrition, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO, USA
| | - Kartik Shankar
- Department of Pediatrics, Section of Nutrition, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO, USA
| | - John P Thyfault
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.,Research Service, Kansas City Veterans Affairs Medical Center, Kansas City, MO, USA.,Center for Children's Healthy Lifestyles and Nutrition, Kansas City, MO, USA.,University of Kansas Diabetes Institute, Kansas City, KS, USA.,Kansas Center for Metabolism and Obesity Research, Kansas City, KS, USA.,Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Kansas Medical Center, Kansas City, KS, USA
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26
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Tong J, Zeng Y, Xie J, Xiao K, Li M, Cong L. Association between flavonoid and subclasses intake and metabolic associated fatty liver disease in U.S. adults: Results from National Health and Nutrition Examination Survey 2017-2018. Front Nutr 2022; 9:1074494. [PMID: 36532560 PMCID: PMC9751205 DOI: 10.3389/fnut.2022.1074494] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 11/14/2022] [Indexed: 07/22/2023] Open
Abstract
BACKGROUND Metabolic associated fatty liver disease (MAFLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Flavonoid is considered a promising candidate for metabolic disease prevention although few studies have explored the relationship between flavonoid intake and MAFLD. PURPOSE To assess the relationship between flavonoid intake and MAFLD prevalence in the U.S. adult population. MATERIALS AND METHODS The data of this cross-sectional study was obtained from National Health and Nutrition Examination Survey (NHANES) and Food and Nutrient Database for Dietary Studies (FNDDS) 2017-2018. Flavonoid and subclasses intake was assessed by two 24h recalls. MAFLD was diagnosed according to the consensus definitions. Multivariate logistic regression model was performed to examine the association between flavonoid intake and MAFLD with adjustments for confounders. RESULTS A total of 4,431 participants were included in this cross-sectional analysis. MAFLD had a weighted prevalence of 41.93% and was not associated with total flavonoid intake. A higher anthocyanin and isoflavone intake, on the other hand, was associated with a lower prevalence of MAFLD. The protective effect of higher anthocyanin intake was significant among male, Non-Hispanic White, and Non-Hispanic Asia participants. Higher isoflavone intake was associated with a lower risk of MAFLD in participants of younger (age < 50), Non-Hispanic Black, Non-Hispanic Asia, and higher HEI-2015 scores compared with the lowest quartile of isoflavone intake. Stratified analysis showed that compared with the lowest quartile of anthocyanin intake, the effect of anthocyanin intake on MAFLD varied by racial groups (P interaction = 0.02). A positive correlation existed between HDL and anthocyanidin intake (P = 0.03), whereas a negative correlation existed between FPG and isoflavone intake (P = 0.02). CONCLUSION MAFLD was adversely linked with flavonoid subclasses, anthocyanin and isoflavone. This modifiable lifestyle provides a potential opportunity to prevent MAFLD. These findings promote future research into the links and mechanisms between anthocyanin and isoflavone intake and MAFLD.
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Affiliation(s)
- Junlu Tong
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Yingjuan Zeng
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Jianhui Xie
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Kecen Xiao
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Man Li
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China
- Center for Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Li Cong
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
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Le MH, Yeo YH, Li X, Li J, Zou B, Wu Y, Ye Q, Huang DQ, Zhao C, Zhang J, Liu C, Chang N, Xing F, Yan S, Wan ZH, Tang NSY, Mayumi M, Liu X, Liu C, Rui F, Yang H, Yang Y, Jin R, Le RHX, Xu Y, Le DM, Barnett S, Stave CD, Cheung R, Zhu Q, Nguyen MH. 2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2022; 20:2809-2817.e28. [PMID: 34890795 DOI: 10.1016/j.cgh.2021.12.002] [Citation(s) in RCA: 361] [Impact Index Per Article: 120.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 11/25/2021] [Accepted: 12/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD. METHODS Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence. RESULTS We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% confidence interval [CI], 28.6%-31.1%); of these, 82.5% of included articles used ultrasound to diagnose NAFLD, with prevalence of 30.6% (95% CI, 29.2%-32.0%). South America (3 studies, 5716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI, 34.0%-37.5%) and 35.3% (95% CI, 25.4%-45.9%), respectively. From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to 37.3% (yearly increase of 0.7%, P < .0001), with South America showing the most rapid change of 2.7% per year, followed by Europe at 1.1%. CONCLUSIONS Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work toward reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.
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Affiliation(s)
- Michael H Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Xiaohe Li
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of Infectious Disease, The Third People's Hospital of Shenzhen, Shenzhen, China
| | - Jie Li
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Biyao Zou
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California
| | - Yuankai Wu
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qing Ye
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; The Third Central Clinical College of Tianjin Medical University, Tianjin; Department of Hepatology of The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Artificial Cells, Tianjin, China
| | - Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine and Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Changqing Zhao
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of T.C.M., Shanghai, China
| | - Jie Zhang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Chenxi Liu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Na Chang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Feng Xing
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of T.C.M., Shanghai, China
| | - Shiping Yan
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Zi Hui Wan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Natasha Sook Yee Tang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Maeda Mayumi
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Xinting Liu
- Medical School of Chinese People's Liberation Army, Beijing, and Department of Pediatrics, the First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Chuanli Liu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Fajuan Rui
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Hongli Yang
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Yao Yang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Ruichun Jin
- Jining Medical University, Jining, Shandong, China
| | - Richard H X Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yayun Xu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - David M Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Scott Barnett
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | | | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California.
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Pafili K, Paschou SA, Armeni E, Polyzos SA, Goulis DG, Lambrinoudaki I. Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones. J Endocrinol Invest 2022; 45:1609-1623. [PMID: 35303270 DOI: 10.1007/s40618-022-01766-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 02/09/2022] [Indexed: 12/12/2022]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) differs between various stages of the female lifespan. The aim of this review is to summarize current evidence on the association of NAFLD and circulating sex hormones and to explore the pathogenesis of NAFLD within the context of (1) sex hormone changes during the reproductive, post-reproductive female life and beyond and (2) the in vitro and in vivo evidence on pharmacological modulation in women on menopausal hormone treatment (MHT) or endocrine therapy after breast cancer. The fluctuation in estrogen concentrations, the relative androgen excess, and the age-related reduction in sex hormone-binding globulin are related to increased NAFLD risk. Moreover, the peri-menopausal changes in body composition and insulin resistance might contribute to the increased NAFLD risk. Whether MHT prevents or improves NAFLD in this population remains an open question. Studies in women with breast cancer treated with tamoxifen or non-steroidal aromatase inhibitors point to their adverse effects on NAFLD development, although a more pronounced effect of tamoxifen is reported. Future studies focusing on the underlying pathogenesis should identify subgroups with the highest risk of NAFLD development and progression into more aggressive forms, as well as elucidate the role of hormone therapies, such as MHT.
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Affiliation(s)
- K Pafili
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, Munich-Neuherberg, Germany
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - S A Paschou
- Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Menopause Unit, 2nd Department of Obstetrics and Gynecology, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - E Armeni
- Menopause Unit, 2nd Department of Obstetrics and Gynecology, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - S A Polyzos
- First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloníki, Greece
| | - D G Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloníki, Greece
| | - I Lambrinoudaki
- Menopause Unit, 2nd Department of Obstetrics and Gynecology, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
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Insight into Potential Interactions of Thyroid Hormones, Sex Hormones and Their Stimulating Hormones in the Development of Non-Alcoholic Fatty Liver Disease. Metabolites 2022; 12:metabo12080718. [PMID: 36005590 PMCID: PMC9414490 DOI: 10.3390/metabo12080718] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 07/30/2022] [Accepted: 07/31/2022] [Indexed: 02/01/2023] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common manifestation of metabolic syndrome. In addition to lifestyle, endocrine hormones play a role in the dysregulation of hepatic metabolism. The most common endocrine hormones contributing to metabolic syndrome are alterations in the levels of thyroid hormones (THs, predominantly in subclinical hypothyroidism) and of sex hormones (in menopause). These hormonal changes influence hepatic lipid and glucose metabolism and may increase hepatic fat accumulation. This review compares the effects of sex hormones, THs and the respective stimulating hormones, Thyroid-Stimulating Hormone (TSH) and Follicle-Stimulating Hormone (FSH), on the development of hepatosteatosis. TSH and FSH may be more relevant to the dysregulation of hepatic metabolism than the peripheral hormones because metabolic changes were identified when only levels of the stimulating hormones were abnormal and the peripheral hormones were still in the reference range. Increased TSH and FSH levels appear to have additive effects on the development of NAFLD and to act independently from each other.
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Wang R, Xue F, Wang L, Shi G, Qian G, Yang N, Chen X. Serum uric acid to creatinine ratio is associated with higher prevalence of NAFLD detected by FibroScan in the United States. J Clin Lab Anal 2022; 36:e24590. [PMID: 35808891 PMCID: PMC9396182 DOI: 10.1002/jcla.24590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 11/23/2022] Open
Abstract
Background The association between the serum uric acid (sUA) to creatinine ratio (sUA/Cr) and non‐alcoholic fatty liver disease (NAFLD) has not been sufficiently clarified. In this study, we investigated the relationship between sUA/Cr and NAFLD among participants in the United States. Methods We performed a cross‐sectional study based on data from the National Health and Nutrition examination Survey (NHANES) 2017–2018. A measured controlled attenuation parameter (CAP) value of ≥274 dB/m detected by Fibroscan was used to identify hepatic steatosis. SUA/Cr was calculated as sUA divided by serum creatinine. Multivariate logistic regression analysis was used to estimate the association between sUA/Cr and NAFLD. The adjusted odds ratio (OR) of sUA/Cr for NAFLD was estimated, and subgroup analysis stratified by sex was also conducted. The nonlinear relationship between sUA/Cr and NAFLD was further described using smooth curve fittings and threshold‐effect analysis. Results We found that sUA/Cr was positively correlated with NAFLD status after fully adjustment for confounding factors. In subgroup analysis stratified by sex, the positive interaction between sUA/Cr and NAFLD status only existed in women but not in men. Moreover, the nonlinear association between sUA/Cr and NAFLD status was an inverted U‐shaped curve with an inflection point at 9.7 among men. Conclusions Our study identified that sUA/Cr was positively associated with the risk of NAFLD among individuals in the United States. Moreover, the correlation between sUA/Cr and NAFLD differed according to sex.
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Affiliation(s)
- Rusha Wang
- Department of Infectious Diseases, Ningbo First Hospital, Ningo University, Ningbo, China
| | - Feiben Xue
- Department of Infectious Diseases, Ningbo First Hospital, Ningo University, Ningbo, China
| | - Liping Wang
- Department of Infectious Diseases, Ningbo First Hospital, Ningo University, Ningbo, China
| | - Guangxia Shi
- Department of Infectious Diseases, Ningbo First Hospital, Ningo University, Ningbo, China
| | - Guoqing Qian
- Department of Infectious Diseases, Ningbo First Hospital, Ningo University, Ningbo, China
| | - Naibin Yang
- Department of Infectious Diseases, Ningbo First Hospital, Ningo University, Ningbo, China
| | - Xueqin Chen
- Department of Traditional Chinese Medicine, Ningbo First Hospital, Ningbo University, Ningbo, China
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Carrieri L, Osella AR, Ciccacci F, Giannelli G, Scavo MP. Premenopausal Syndrome and NAFLD: A New Approach Based on Gender Medicine. Biomedicines 2022; 10:1184. [PMID: 35625920 PMCID: PMC9138606 DOI: 10.3390/biomedicines10051184] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/18/2022] [Accepted: 05/19/2022] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition that affects 25% of the world's population. There is a clear difference in both geographical distribution and sex in childbearing age. These differences are reduced when women become older and senescence begins. The factors that affect the likelihood of developing NAFLD in a premenopausal woman are an imbalance of sex hormones (especially in estradiol and androgen), microbiome dysregulation, insulin resistance, early menarche, the length of time that the woman breastfeeds for and polycystic ovarian syndrome (PCOS). The aim of this review is to identify various physical ailments that may not appear to be serious to young women but that then affect the onset of NAFLD in perimenopause and can degenerate into NASH. These conditions should also be considered in future clinical management, as well as in research opportunities, in order to customize the monitoring and treatment of NAFLD, considering gender medicine for those women who had early metabolic symptoms that were not considered to be significant at the time.
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Affiliation(s)
- Livianna Carrieri
- Personalized Medicine Laboratory, National Institute of Gastroenterology IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
| | - Alberto Ruben Osella
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
| | - Fausto Ciccacci
- UniCamillus Saint Camillus International, University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy;
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
| | - Maria Principia Scavo
- Personalized Medicine Laboratory, National Institute of Gastroenterology IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
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Schmid A, Arians M, Karrasch T, Pons-Kühnemann J, Schäffler A, Roderfeld M, Roeb E. Improvement of Type 2 Diabetes Mellitus and Attenuation of NAFLD Are Associated with the Success of Obesity Therapy. J Clin Med 2022; 11:jcm11071756. [PMID: 35407364 PMCID: PMC8999703 DOI: 10.3390/jcm11071756] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 03/16/2022] [Indexed: 12/13/2022] Open
Abstract
Obesity and type 2 diabetes mellitus (T2D) represent important comorbidities of the metabolic syndrome, which are associated with non-alcoholic fatty liver disease (NAFLD)-related hepatic fibrosis. In total, 160 morbidly obese patients-81 following a low-calorie formula diet (LCD) program and 79 undergoing bariatric surgery (Roux-en-Y gastric bypass, RYGB)-were examined for anthropometric and metabolic parameters at base-line and during 12 months of weight loss, focusing on a putative co-regulation of T2D parameters and liver fibrosis risk. High NAFLD fibrosis scores (NFS) before intervention were associated with elevated HbA1c levels and T2D. Loss of weight and body fat percentage (BFL) were associated with improved glucose and lipid metabolism and reduced risk of NAFLD-related fibrosis, with particularly beneficial effects by RYGB. Both T2D improvement and NFS decrease were positively associated with high BFL. A highly significant correlation of NFS reduction with BFL was restricted to male patients while being absent in females, accompanied by generally higher BFL in men. Overall, the data display the relation of BFL, T2D improvement, and reduced NAFLD-related fibrosis risk during weight loss in morbidly obese individuals induced by diet or RYGB. Furthermore, our data suggest a considerable sexual dimorphism concerning the correlation of fat loss and improved risk of liver fibrosis.
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Affiliation(s)
- Andreas Schmid
- Department of Internal Medicine III, Justus Liebig University, 35392 Giessen, Germany; (A.S.); (T.K.); (A.S.)
| | - Miriam Arians
- Department of Gastroenterology, Internal Medicine II, Justus Liebig University, Klinikstr. 33, 35392 Giessen, Germany; (M.A.); (M.R.)
| | - Thomas Karrasch
- Department of Internal Medicine III, Justus Liebig University, 35392 Giessen, Germany; (A.S.); (T.K.); (A.S.)
| | - Jörn Pons-Kühnemann
- Institute of Medical Informatics, Justus Liebig University, 35392 Giessen, Germany;
| | - Andreas Schäffler
- Department of Internal Medicine III, Justus Liebig University, 35392 Giessen, Germany; (A.S.); (T.K.); (A.S.)
| | - Martin Roderfeld
- Department of Gastroenterology, Internal Medicine II, Justus Liebig University, Klinikstr. 33, 35392 Giessen, Germany; (M.A.); (M.R.)
| | - Elke Roeb
- Department of Gastroenterology, Internal Medicine II, Justus Liebig University, Klinikstr. 33, 35392 Giessen, Germany; (M.A.); (M.R.)
- Correspondence:
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Mirshahi F, Aqbi HF, Isbell M, Manjili SH, Guo C, Saneshaw M, Dozmorov M, Khosla A, Wack K, Carrasco-Zevallos OM, Idowu MO, Wang XY, Sanyal AJ, Manjili MH, Bandyopadhyay D. Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma. Cell Rep 2022; 38:110454. [PMID: 35235789 PMCID: PMC9028248 DOI: 10.1016/j.celrep.2022.110454] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 01/27/2022] [Accepted: 02/04/2022] [Indexed: 12/30/2022] Open
Abstract
To discover distinct immune responses promoting or inhibiting hepatocellular carcinoma (HCC), we perform a three-dimensional analysis of the immune cells, correlating immune cell types, interactions, and changes over time in an animal model displaying gender disparity in nonalcoholic fatty liver disease (NAFLD)-associated HCC. In response to a Western diet (WD), animals mount acute and chronic patterns of inflammatory cytokines, respectively. Tumor progression in males and females is associated with a predominant CD8+ > CD4+, Th1 > Th17 > Th2, NKT > NK, M1 > M2 pattern in the liver. A complete rescue of females from HCC is associated with an equilibrium Th1 = Th17 = Th2, NKT = NK, M1 = M2 pattern, while a partial rescue of males from HCC is associated with an equilibrium CD8+ = CD4+, NKT = NK and a semi-equilibrium Th1 = Th17 > Th2 but a sustained M1 > M2 pattern in the liver. Our data suggest that immunological pattern-recognition can explain immunobiology of HCC and guide immune modulatory interventions for the treatment of HCC in a gender-specific manner. Mirshahi et al. performed a three-dimensional analysis of hepatic and splenic immune cells, correlating the immune cell types, their interactions and proportions, and changes over time. They discover gender-associated immunological patterns determining tumor progression, as well as partial or complete inhibition of hepatocellular carcinoma.
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Affiliation(s)
- Faridoddin Mirshahi
- Department of Internal Medicine, VCU School of Medicine, Richmond, VA 23298, USA
| | - Hussein F Aqbi
- Department of Internal Medicine, VCU School of Medicine, Richmond, VA 23298, USA; VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA; College of Science, Mustansiriyah University, Baghdad, Iraq
| | - Madison Isbell
- Department of Microbiology & Immunology, VCU School of Medicine, Richmond, VA 23298, USA
| | - Saeed H Manjili
- Department of Internal Medicine, VCU School of Medicine, Richmond, VA 23298, USA
| | - Chunqing Guo
- Department of Human & Molecular Genetics, VCU School of Medicine, Richmond, VA 23298, USA
| | - Mulugeta Saneshaw
- VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA
| | - Mikhail Dozmorov
- VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA; Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USA
| | | | | | | | - Michael O Idowu
- VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA; Department of Pathology, VCU School of Medicine, Richmond, VA 23298, USA
| | - Xiang-Yang Wang
- VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA; Department of Human & Molecular Genetics, VCU School of Medicine, Richmond, VA 23298, USA; Hunter Holmes McGuire VA Medical Center, Richmond, VA 23298, USA
| | - Arun J Sanyal
- Department of Internal Medicine, VCU School of Medicine, Richmond, VA 23298, USA; VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA.
| | - Masoud H Manjili
- Department of Microbiology & Immunology, VCU School of Medicine, Richmond, VA 23298, USA; VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA; Department of Pathology, VCU School of Medicine, Richmond, VA 23298, USA.
| | - Dipankar Bandyopadhyay
- VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA; Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USA
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Fang D, Tang W, Zhao X, Sun H, Gu T, Bi Y. Gender differences in the association of body composition and biopsy-proved nonalcoholic steatohepatitis. Hepatol Int 2022; 16:337-347. [PMID: 35201574 DOI: 10.1007/s12072-021-10265-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 10/20/2021] [Indexed: 11/04/2022]
Abstract
BACKGROUND AND AIM Body composition was associated with nonalcoholic steatohepatitis (NASH), but results were controversial probably due to gender differences. Hence, we aim to explore the association of body composition and NASH in males and females. METHODS We conducted a cross-sectional analysis of obese subjects undergone liver biopsy. According to NASH Clinical Research Network system, subjects were categorized as Normal Control (NC), non-NASH or NASH. Body composition was accessed by dual-energy X-ray absorptiometry. RESULTS This study enrolled 336 subjects (mean age 32.0 years, mean BMI 39.15 kg/m2, female, 64.0%). Males have lower relative muscle mass (RMM 55.21 ± 4.07%) and females have higher android to gynoid ratio (AGR, 0.82 ± 0.21) in NASH when compared with non-NASH (RMM 57.49 ± 4.75%; AGR 0.7 ± 0.15) and NC (RMM 58.69 ± 4.09%; AGR 0.66 ± 0.19, p < 0.05 for each). After adjusting for confounding factors, low RMM was the independent risk factor for NASH in males (odds ratio [OR] 0.550; 95% confidence interval [CI] 0.312-0.970), high AGR was the independent risk factor for NASH in females (OR 1.694; 95% CI 1.073-2.674). Further, RMM in males and AGR in females, respectively, was associated with liver steatosis and activity, but not with fibrosis. ROC curve revealed that the optimal cutoff value of RMM was 58.09% in males and AGR was 0.92 in females for predicting NASH. CONCLUSIONS We firstly revealed that low RMM and high AGR were the independent risk factors for NASH in males and females, respectively, indicating that sex-specific interventions for improving body composition may reduce the risk of NASH in obese subjects.
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Affiliation(s)
- Da Fang
- Department of Endocrinology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Wenjuan Tang
- Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoyu Zhao
- Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Haixiang Sun
- Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Tianwei Gu
- Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
| | - Yan Bi
- Department of Endocrinology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China. .,Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
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Chen XY, Wang C, Huang YZ, Zhang LL. Nonalcoholic fatty liver disease shows significant sex dimorphism. World J Clin Cases 2022; 10:1457-1472. [PMID: 35211584 PMCID: PMC8855265 DOI: 10.12998/wjcc.v10.i5.1457] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 12/02/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), which has been renamed metabolic dysfunction-associated fatty liver disease, is a growing global medical problem. The incidence of NAFLD and its associated end-stage liver disease is increasing each year, and many research advancements have been achieved to date. This review focuses on the current knowledge of the sex differences in NAFLD and does not elaborate on areas without differences. Studies have revealed significant sex differences in the prevalence, influencing factors, pathophysiology, complications and therapies of NAFLD. Men have a higher incidence than women. Compared with women, men exhibit increased visceral fat deposition, are more susceptible to leptin resistance, lack estrogen receptors, and tend to synthesize fatty acids into fat storage. Male patients will experience more severe hepatic fibrosis and a higher incidence of liver cancer. However, once NAFLD occurs, women show a faster progression of liver fibrosis, higher levels of liver cell damage and inflammation and are less likely to undergo liver transplantation than men. In general, men have more risk factors and more severe pathophysiological reactions than women, whereas the development of NAFLD is faster in women, and the treatments for women are more limited than those for men. Thus, whether sex differences should be considered in the individualized prevention and treatment of NAFLD in the future is worth considering.
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Affiliation(s)
- Xing-Yu Chen
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Cong Wang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Yi-Zhou Huang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Li-Li Zhang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
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Lee C, Kim J, Han J, Oh D, Kim M, Jeong H, Kim TJ, Kim SW, Kim JN, Seo YS, Suzuki A, Kim JH, Jung Y. Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis. Nat Commun 2022; 13:578. [PMID: 35102146 PMCID: PMC8803937 DOI: 10.1038/s41467-022-28138-6] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 01/12/2022] [Indexed: 12/21/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an important health concern worldwide and progresses into nonalcoholic steatohepatitis (NASH). Although prevalence and severity of NAFLD/NASH are higher in men than premenopausal women, it remains unclear how sex affects NAFLD/NASH pathophysiology. Formyl peptide receptor 2 (FPR2) modulates inflammatory responses in several organs; however, its role in the liver is unknown. Here we show that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH. NASH-like liver injury was induced in both sexes during choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) feeding, but compared with females, male mice had more severe hepatic damage. Fpr2 was more highly expressed in hepatocytes and healthy livers from females than males, and FPR2 deletion exacerbated liver damage in CDAHFD-fed female mice. Estradiol induced Fpr2 expression, which protected hepatocytes and the liver from damage. In conclusion, our results demonstrate that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH, suggesting a novel therapeutic target for NAFLD/NASH.
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Affiliation(s)
- Chanbin Lee
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Jieun Kim
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Jinsol Han
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Dayoung Oh
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Minju Kim
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Hayeong Jeong
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Tae-Jin Kim
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
- Department of Biological Sciences, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Sang-Woo Kim
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
- Department of Biological Sciences, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Jeong Nam Kim
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
- Department of Microbiology, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Young-Su Seo
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
- Department of Microbiology, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea
| | - Ayako Suzuki
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
| | - Jae Ho Kim
- Department of Physiology, Pusan National University School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea
| | - Youngmi Jung
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea.
- Department of Biological Sciences, College of Natural Science, Pusan National University, Pusan, 46241, Republic of Korea.
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Zhang Y, Fu T, Yuan XJ, Ye YC, Guo ZW, Liu K, Ji ZH, Shao ZJ. Analyzing the Spatiotemporal Distribution and Characteristics of Liver Cirrhosis in Hospitalized Patients in Wuwei, Gansu Province During 1995-2016: A Long-Term Retrospective Study. Front Physiol 2022; 13:845095. [PMID: 35392371 PMCID: PMC8980317 DOI: 10.3389/fphys.2022.845095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 03/07/2022] [Indexed: 12/09/2022] Open
Abstract
Objectives: This was a long-term retrospective study, aiming to understand the temporal and spatial trend of cirrhosis in Wuwei from 1995 to 2016, explore its spatio-temporal aggregation, and find out the high incidence areas. To provide theoretical basis for the formulation of comprehensive prevention and treatment strategy of cirrhosis in Wuwei. Methods: Herein, we extracted data of cirrhosis patients who were treated in 12 sentinel hospitals in Wuwei from their medical records. We used SAS and Joinpoint Regression Program for data analysis, SaTScan 9.4 software for clustering area detection, and ArcGIS 10.2 software for geographical distribution mapping. Results: Among 3308 patients with liver cirrhosis (average age, 55.34 years) included in this study, 15.9% were aged 50-54 years. The majority were men (2716, 65.8%), with a sex ratio of 1.92:1 and peasants by occupation (1369, 60.3%). The basic social medical insurance system covered the healthcare costs of 1271 patients (63%). A Joinpoint regression analysis done for 1995-2016 revealed an increase in the standardized cirrhosis rate [average annual percent change (AAPC) = 16.7% (95% CI, 10.2-23.5%)] with three joinpoints in 2010, 2013, and 2016. The annual percent change (APC) from 1995 to 2010 was 11.13% (95% CI: 6.5-16.0), and APC from 2010 to 2013 was 66.48% (95% CI:16.0-138.9); conversely, from 2013 to 2016, APC was 4.4% (95% CI, -7.5-17.8%). Hongshagang Town showed the highest average incidence. Each township showed a gradual increase in the incidence after 2010. The results revealed that in each township, liver cirrhosis incidence had some spatial aggregation and was nonrandom. Four liver cirrhosis clusters were noted in 75 townships in Wuwei. Data were gathered from 2011 to 2016. Conclusions: From 1995 to 2016, the incidence of cirrhosis in Wuwei still showed an increasing trend, but the growth rate slowed down since 2013. In Wuwei, the rate of standardization of cirrhosis in female patients increased steadily and faster than in male patients. It is necessary to strengthen the diagnosis, treatment, prevention, and control measures of cirrhosis-related diseases. The results of spatial scanning, basic spatial distribution, aggregation time, and time trend analysis were consistent.
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Affiliation(s)
- Yang Zhang
- Department of Epidemiology, School of Public Health, Air Force Medical University, Xi’an, China
- Shaanxi Energy Institute, College of Nursing, Xi’an, China
- Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi’an, China
- *Correspondence: Yang Zhang, ; Zhong-Jun Shao, ; Zhao-Hua Ji,
| | - Ting Fu
- Department of Epidemiology, School of Public Health, Air Force Medical University, Xi’an, China
- Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi’an, China
| | - Xiao-Jie Yuan
- Department of Epidemiology, School of Public Health, Air Force Medical University, Xi’an, China
- Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi’an, China
| | | | - Zhi-Wen Guo
- Department of Infection Disease Control and Prevention, Wu Wei Center for Disease Prevention and Control, Wuwei, China
| | - Kun Liu
- Department of Epidemiology, School of Public Health, Air Force Medical University, Xi’an, China
- Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi’an, China
| | - Zhao-Hua Ji
- Department of Epidemiology, School of Public Health, Air Force Medical University, Xi’an, China
- Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi’an, China
- *Correspondence: Yang Zhang, ; Zhong-Jun Shao, ; Zhao-Hua Ji,
| | - Zhong-Jun Shao
- Department of Epidemiology, School of Public Health, Air Force Medical University, Xi’an, China
- Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi’an, China
- *Correspondence: Yang Zhang, ; Zhong-Jun Shao, ; Zhao-Hua Ji,
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Shaheen M, Schrode KM, Pan D, Kermah D, Puri V, Zarrinpar A, Elisha D, Najjar SM, Friedman TC. Sex-Specific Differences in the Association Between Race/Ethnicity and NAFLD Among US Population. Front Med (Lausanne) 2021; 8:795421. [PMID: 34926533 PMCID: PMC8674562 DOI: 10.3389/fmed.2021.795421] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 11/08/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is spreading worldwide, with a racial/ethnic disparity. We examined the gender role in the racial/ethnic difference in NAFLD in the US population. We analyzed data for 3,292 individuals ≥18 years old from NHANES 2017-2018, a representative sample of the non-institutionalized adult population in the US. Exclusions were subjects with elevated transferrin level, chronic hepatitis B or C, excessive alcohol use, or prescription medications that might cause hepatic steatosis. NAFLD was diagnosed by FibroScan® using controlled attenuation parameter (CAP) values: S0 <238, S1 = 238-259, S2 = 260-290, S3 >290. Data were analyzed using Chi square and multinomial regression. The overall prevalence of NAFLD was 47.9% [S2 = 16.1%, and S3 = 31.8%]. The prevalence of S3 was highest among Mexican Americans (46%), lowest among Blacks (22.7%), 29.9% in other Hispanics and 32.1% in Whites (p < 0.05). It was higher among Mexican American males (54.1%) compared to Mexican American females (37.7%) (p < 0.05). In the adjusted model, Mexican Americans were two times more likely than Whites to have S2 and S3 (p < 0.05). Only male Mexican Americans had higher odds of S2 and S3 relative to male White (p < 0.05). Males had higher odds of S3 relative to non-menopausal females (p < 0.05). There was no difference in the odds of S2 or S3 NAFLD among the menopausal females with or without hormone therapy relative to non-menopausal females (p > 0.05). While Mexican Americans had the highest prevalence of severe NAFLD relative to the other racial/ethnic groups, only male Mexican Americans, but not females, had higher likelihood of both moderate and severe NAFLD relative to Whites. Interventions that specifically target Mexican American males are needed to increase awareness about NAFLD and its prevention.
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Affiliation(s)
- Magda Shaheen
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Katrina M. Schrode
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Deyu Pan
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Dulcie Kermah
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Vishwajeet Puri
- Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States
| | - Ali Zarrinpar
- University of Florida College of Medicine, Gainesville, FL, United States
| | - David Elisha
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Sonia M. Najjar
- Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States
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Alam S, Eslam M, SKM Hasan N, Anam K, Chowdhury MAB, Khan MAS, Hasan MJ, Mohamed R. Risk factors of nonalcoholic fatty liver disease in lean body mass population: A systematic review and meta-analysis. JGH Open 2021; 5:1236-1249. [PMID: 34816009 PMCID: PMC8593777 DOI: 10.1002/jgh3.12658] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 08/05/2021] [Accepted: 09/10/2021] [Indexed: 12/20/2022]
Abstract
The pathophysiology and risk factors of nonalcoholic fatty liver disease (NAFLD) among lean patients is poorly understood and therefore investigated. We performed a meta-analysis of observational studies. Of 1175 articles found through searching from Medline/PubMed, Banglajol, and Google Scholar by two independent investigators, 22 were selected. Data from lean (n = 6768) and obese (n = 9253) patients with NAFLD were analyzed; lean (n = 43 398) and obese (n = 9619) subjects without NAFLD served as controls. Age, body mass index, waist circumference, systolic blood pressure, and diastolic blood pressure (DBP) had significantly higher estimates in lean NAFLD patients than in lean non-NAFLD controls. Fasting blood sugar [MD(mean difference) 5.17 mg/dl, 95% CI(confidence interval) 4.14-6.16], HbA1c [MD 0.29%, 95% CI 0.11-0.48], and insulin resistance [HOMA-IR] [MD 0.49 U, 95% CI 0.29-0.68]) were higher in lean NAFLD patients than in lean non-NAFLD controls. All components of the lipid profile were raised significantly in the former group except high-density lipoprotein. An increased uric acid (UA) level was found to be associated with the presence of NAFLD among lean. Cardio-metabolic profiles of nonlean NAFLD patients significantly differs from the counter group. However, the magnitude of the difference of lipid and glycemic profile barely reached statistical significance when subjects were grouped according to lean and nonlean NAFLD. But DBP (slope: 0.19, P < 0.037), HOMA-IR (slope: 0.58, P < 0.001), and UA (slope: 0.36, P = 0.022) were significantly higher if NAFLD was present compared to that of non-NAFLD group. Lean and nonlean NAFLD patients are metabolically similar and share common risk factors.
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Affiliation(s)
- Shahinul Alam
- Department of HepatologyBangabandhu Sheikh Mujib Medical UniversityDhakaBangladesh
| | - Mohammad Eslam
- Storr Liver Centre, Westmead Institute for Medical ResearchWestmead Hospital and University of SydneySydneyNew South WalesAustralia
| | - Nazmul SKM Hasan
- Department of HepatologyShaheed Syed Nazrul Islam Medical CollegeKishoreganjBangladesh
| | - Kamrul Anam
- Department of Medical GastroenterologySheikh Russel National Gastroliver Institute and HospitalDhakaBangladesh
| | | | - Md Abdullah Saeed Khan
- Meta analysis DivisionPi Research Consultancy CenterDhakaBangladesh
- Department of PharmacologyShaheed Sayed Nazrul Islam Medical CollegeKishoreganjBangladesh
| | - Mohammad J Hasan
- Meta analysis DivisionPi Research Consultancy CenterDhakaBangladesh
| | - Rosmawati Mohamed
- Department of MedicineUniversity Malaya Medical CentreKuala LumpurMalaysia
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Xie F, Pei Y, Zhou Q, Cao D, Wang Y. Comparison of obesity-related indices for identifying nonalcoholic fatty liver disease: a population-based cross-sectional study in China. Lipids Health Dis 2021; 20:132. [PMID: 34629056 PMCID: PMC8502306 DOI: 10.1186/s12944-021-01560-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 09/14/2021] [Indexed: 12/18/2022] Open
Abstract
Background The relationship between nonalcoholic fatty liver disease (NAFLD) and obesity-related indices has been analyzed separately thus far, and evidence comparing these indices together is still lacking, especially in China. This study aimed to comprehensively evaluate the predictive performance of anthropometric and metabolic indices to identify NAFLD in Chinese adults. Methods This study recruited a total of 1748 participants who were 18 years or older in southeastern China. The systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL), waist circumference (WC), a body shape index (ABSI), atherogenic index of plasma (AIP), abdominal volume index (AVI), body adiposity index (BAI), body mass index (BMI), body roundness index (BRI), conicity index (CI), triglyceride glucose (TyG), waist hip ratio (WHR), and waist height ratio (WHtR) were measured. The association between these indices and NAFLD was analyzed via logistic analyses with odds ratios (ORs). Receiver operating characteristic (ROC) curves and areas under the curve (AUCs) were used to compare the predictive performance of these indices to identify NAFLD. Results BMI had the greatest total AUC (AUC = 0.841) in the ROC curve analysis. However, BRI and BMI both had the best diagnostic ability in males (AUC = 0.812), and BRI had the best diagnostic ability in females (AUC = 0.849). Furthermore, AVI had the greatest AUC for patients who were ~ 20 (AUC = 0.892) and ~ 40 years old (AUC = 0.831), while TyG showed a higher predictive ability than AVI in those who were ~ 60 years old (AUC = 0.766). Conclusion This study identified sex- and age-specific indices for predicting NAFLD in Chinese subjects. Compared with indices for all age groups, sex- and age-specific indices can provide more accurate assistance for clinical diagnosis and treatment. Supplementary Information The online version contains supplementary material available at 10.1186/s12944-021-01560-3.
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Affiliation(s)
- Fangfei Xie
- Physical Examination Center, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People's Republic of China.
| | - Yuyu Pei
- Physical Examination Center, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People's Republic of China
| | - Quan Zhou
- Physical Examination Center, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People's Republic of China
| | - Deli Cao
- Physical Examination Center, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People's Republic of China
| | - Yun Wang
- Physical Examination Center, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People's Republic of China
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Kulkarni S, Naz N, Gu H, Stoll JM, Thompson MD, DeBosch BJ. A clinical model to predict fibrosis on liver biopsy in paediatric subjects with nonalcoholic fatty liver disease. Clin Obes 2021; 11:e12472. [PMID: 34106515 PMCID: PMC8928096 DOI: 10.1111/cob.12472] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 05/09/2021] [Accepted: 05/28/2021] [Indexed: 12/19/2022]
Abstract
The incidence of nonalcoholic fatty liver disease (NAFLD) in children is rapidly increasing. Liver fibrosis is a poor prognostic feature that independently predicts cirrhosis. The time that intercedes the first medical encounter and biopsy is rate-limiting to multi-modal treatment. This study aimed to identify non-invasive parameters to predict advanced NAFLD and fibrosis. We conducted a single-center, retrospective 10-year analysis of 640 paediatric patients who underwent liver biopsy. 55 patients, age 3-21 years, had biopsy-confirmed NAFLD. We assessed primary outcomes, NAFLD activity score (NAS) and fibrosis scores, against non-invasive parameters by linear regression, by using binary cutoff values, and by a multivariate logistic regression fibrosis prediction model. NAS correlated with platelets and female sex. Fibrosis scores correlated with platelet counts, gamma glutamyl transferase (GGT), and ultrasound shear wave velocity. 25-hydroxy-vitamin D and GGT differentiated mild versus moderate-to-advanced fibrosis. Our multivariate logistical regression model-based scoring system predicted F2 or higher (parameters: BMI%, vitamin D, platelets, GGT), with sensitivity and specificity of 0.83 and 0.95 (area under the ROC curve, 0.944). We identify a clinical model to identify high-risk patients for expedited biopsy. Stratifying patients to abbreviate time-to-biopsy can attenuate delays in aggressive therapy for high-risk patients.
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Affiliation(s)
- Sakil Kulkarni
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Nadia Naz
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Hongjie Gu
- Department of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
| | - Janis M. Stoll
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Michael D. Thompson
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
- Digestive Diseases Research Center (DDRCC), Washington University School of Medicine, St. Louis, MO, USA
| | - Brian J. DeBosch
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
- Digestive Diseases Research Center (DDRCC), Washington University School of Medicine, St. Louis, MO, USA
- Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA
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Li Q, Xie W, Li L, Wang L, You Q, Chen L, Li J, Ke Y, Fang J, Liu L, Hong H. Development and Validation of a Prediction Model for Elevated Arterial Stiffness in Chinese Patients With Diabetes Using Machine Learning. Front Physiol 2021; 12:714195. [PMID: 34497538 PMCID: PMC8419456 DOI: 10.3389/fphys.2021.714195] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 07/31/2021] [Indexed: 01/21/2023] Open
Abstract
Background Arterial stiffness assessed by pulse wave velocity is a major risk factor for cardiovascular diseases. The incidence of cardiovascular events remains high in diabetics. However, a clinical prediction model for elevated arterial stiffness using machine learning to identify subjects consequently at higher risk remains to be developed. Methods Least absolute shrinkage and selection operator and support vector machine-recursive feature elimination were used for feature selection. Four machine learning algorithms were used to construct a prediction model, and their performance was compared based on the area under the receiver operating characteristic curve metric in a discovery dataset (n = 760). The model with the best performance was selected and validated in an independent dataset (n = 912) from the Dryad Digital Repository (https://doi.org/10.5061/dryad.m484p). To apply our model to clinical practice, we built a free and user-friendly web online tool. Results The predictive model includes the predictors: age, systolic blood pressure, diastolic blood pressure, and body mass index. In the discovery cohort, the gradient boosting-based model outperformed other methods in the elevated arterial stiffness prediction. In the validation cohort, the gradient boosting model showed a good discrimination capacity. A cutoff value of 0.46 for the elevated arterial stiffness risk score in the gradient boosting model resulted in a good specificity (0.813 in the discovery data and 0.761 in the validation data) and sensitivity (0.875 and 0.738, respectively) trade-off points. Conclusion The gradient boosting-based prediction system presents a good classification in elevated arterial stiffness prediction. The web online tool makes our gradient boosting-based model easily accessible for further clinical studies and utilization.
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Affiliation(s)
- Qingqing Li
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Department of Cardiology, Department of Cardiac Surgery, Fujian Heart Disease Center, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China
| | - Wenhui Xie
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Department of Cardiology, Department of Cardiac Surgery, Fujian Heart Disease Center, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China
| | - Liping Li
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Department of Cardiology, Department of Cardiac Surgery, Fujian Heart Disease Center, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China
| | - Lijing Wang
- Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Qinyi You
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Department of Cardiology, Department of Cardiac Surgery, Fujian Heart Disease Center, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China
| | - Lu Chen
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Department of Cardiology, Department of Cardiac Surgery, Fujian Heart Disease Center, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jing Li
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Department of Cardiology, Department of Cardiac Surgery, Fujian Heart Disease Center, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yilang Ke
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Department of Cardiology, Department of Cardiac Surgery, Fujian Heart Disease Center, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jun Fang
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Department of Cardiology, Department of Cardiac Surgery, Fujian Heart Disease Center, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China
| | - Libin Liu
- Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Huashan Hong
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Department of Cardiology, Department of Cardiac Surgery, Fujian Heart Disease Center, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China
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Robeva R, Mladenović D, Vesković M, Hrnčić D, Bjekić-Macut J, Stanojlović O, Livadas S, Yildiz BO, Macut D. The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause. Maturitas 2021; 151:22-30. [PMID: 34446275 DOI: 10.1016/j.maturitas.2021.06.012] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/18/2021] [Accepted: 06/26/2021] [Indexed: 12/12/2022]
Abstract
The hypoestrogenic period after menopause and associated metabolic imbalance might facilitate the onset of non-alcoholic fatty liver disease (NAFLD) and its progression. The prevalence of NAFLD increases in patients experiencing premature ovarian insufficiency, as well as surgical or natural menopause. The postmenopausal period is characterized by dyslipidemia and insulin resistance associated with an increased influx of free fatty acids to the liver with consequent steatosis and further progression of NAFLD. More than half of postmenopausal women with diabetes mellitus type 2 suffer from NAFLD. It is suggested that estrogens slow the progression of chronic liver diseases by suppression of inflammation, improvement of mitochondrial function, alleviation of oxidative stress, insulin resistance, and fibrogenesis. The hyperandrogenic state of polycystic ovary syndrome (PCOS) is associated with the development of NAFLD in women of reproductive age, but it is difficult to extend these findings to menopause due to inappropriate diagnosis of PCOS after menopause. Lifestyle intervention, including physical activity and dietary regimens, remains the first-line preventive and therapeutic option for NAFLD. There are contradictory reports on the use of menopausal hormonal therapy (MHT) and NAFLD. It is necessary to investigate the potential effects of estradiol dose, progesterone type, selective estrogen receptor modulators and tissue-selective estrogen complex compounds on NAFLD development and progression in postmenopausal women. The present review aims to explore the pathophysiological and clinical aspects of liver metabolic disturbances in women after menopause, focusing on the possible preventive and therapeutic strategies in NAFLD, including the potential role of MHT.
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Affiliation(s)
- Ralitsa Robeva
- Department of Endocrinology, USHATE "Acad. Iv. Penchev", Faculty of Medicine, Medical University-Sofia, Sofia, Bulgaria
| | - Dušan Mladenović
- Institute of Pathophysiology "Ljubodrag Buba Mihailović", Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Milena Vesković
- Institute of Pathophysiology "Ljubodrag Buba Mihailović", Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Dragan Hrnčić
- Institute of Medicinal Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelica Bjekić-Macut
- Department of Endocrinology, CHC Bežanijska kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Olivera Stanojlović
- Institute of Medicinal Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | | | - Bulent O Yildiz
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Djuro Macut
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotića 13, 11000 Belgrade, Serbia.
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Li Q, Xie W, Li L, Wang L, You Q, Chen L, Li J, Ke Y, Fang J, Liu L, Hong H. Development and Validation of a Prediction Model for Elevated Arterial Stiffness in Chinese Patients With Diabetes Using Machine Learning. Front Physiol 2021. [DOI: 10.3389/fphys.2021.714195
expr 962169460 + 908583142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023] Open
Abstract
BackgroundArterial stiffness assessed by pulse wave velocity is a major risk factor for cardiovascular diseases. The incidence of cardiovascular events remains high in diabetics. However, a clinical prediction model for elevated arterial stiffness using machine learning to identify subjects consequently at higher risk remains to be developed.MethodsLeast absolute shrinkage and selection operator and support vector machine-recursive feature elimination were used for feature selection. Four machine learning algorithms were used to construct a prediction model, and their performance was compared based on the area under the receiver operating characteristic curve metric in a discovery dataset (n = 760). The model with the best performance was selected and validated in an independent dataset (n = 912) from the Dryad Digital Repository (https://doi.org/10.5061/dryad.m484p). To apply our model to clinical practice, we built a free and user-friendly web online tool.ResultsThe predictive model includes the predictors: age, systolic blood pressure, diastolic blood pressure, and body mass index. In the discovery cohort, the gradient boosting-based model outperformed other methods in the elevated arterial stiffness prediction. In the validation cohort, the gradient boosting model showed a good discrimination capacity. A cutoff value of 0.46 for the elevated arterial stiffness risk score in the gradient boosting model resulted in a good specificity (0.813 in the discovery data and 0.761 in the validation data) and sensitivity (0.875 and 0.738, respectively) trade-off points.ConclusionThe gradient boosting-based prediction system presents a good classification in elevated arterial stiffness prediction. The web online tool makes our gradient boosting-based model easily accessible for further clinical studies and utilization.
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45
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Burra P, Bizzaro D, Gonta A, Shalaby S, Gambato M, Morelli MC, Trapani S, Floreani A, Marra F, Brunetto MR, Taliani G, Villa E. Clinical impact of sexual dimorphism in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Liver Int 2021; 41:1713-1733. [PMID: 33982400 DOI: 10.1111/liv.14943] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 05/05/2021] [Accepted: 05/06/2021] [Indexed: 12/11/2022]
Abstract
NAFLD/NASH is a sex-dimorphic disease, with a general higher prevalence in men. Women are at reduced risk of NAFLD compared to men in fertile age, whereas after menopause women have a comparable prevalence of NAFLD as men. Indeed, sexual category, sex hormones and gender habits interact with numerous NAFLD factors including cytokines, stress and environmental factors and alter the risk profiles and phenotypes of NAFLD. In the present review, we summarized the last findings about the influence of sex on epidemiology, pathogenesis, progression in cirrhosis, indication for liver transplantation and alternative therapies, including lifestyle modification and pharmacological strategies. We are confident that an appropriate consideration of sex, age, hormonal status and sociocultural gender differences will lead to a better understanding of sex differences in NAFLD risk, therapeutic targets and treatment responses and will aid in achieving sex-specific personalized therapies.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Debora Bizzaro
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Anna Gonta
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Sarah Shalaby
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | | | - Silvia Trapani
- Italian National Transplant Center, Italian National Institute of Health, Rome, Italy
| | - Annarosa Floreani
- University of Padova, Padua, Italy.,IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Maurizia Rossana Brunetto
- Hepatology and Liver Physiopathology Laboratory and Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Gloria Taliani
- Infectious Diseases Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Erica Villa
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
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46
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Wáng YXJ. Gender-specific liver aging and magnetic resonance imaging. Quant Imaging Med Surg 2021; 11:2893-2904. [PMID: 34249621 DOI: 10.21037/qims-21-227] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 04/15/2021] [Indexed: 12/14/2022]
Abstract
The number of imaging studies performed on elderly individuals will increase in the next several decades. It is important to understand normal age-related changes in the structural and functional imaging appearance of the liver. This article highlights a number of liver aging aspects which are particularly relevant to magnetic resonance imaging (MRI). Physiology of aging liver is associated with a reduction in size, in perfusion, and in function. Pulsed echo-Doppler showed substantial reduction of portal flow in elderly subjects, particularly those after the age of 75 years old. An MRI biomarker diffusion derived vessel density (DDVD) demonstrated that liver microperfusion volume in healthy females starts to decrease even before menopause age. Liver fat content and iron content increase with aging, and the change is more substantial in women after menopause. Adult men have higher liver fat and iron contents than women from the start and change less during aging. Nonalcoholic fatty liver disease (NAFLD) is very common among assumed healthy subjects. There is a male predominance of NAFLD from the paediatric population up to fifth decade of life in adults. After the age of 60 years, women overtake their male counterparts in prevalence of NAFLD. Higher liver fat leads to decreased apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM)-Dslow measures. Higher liver iron content shortens T2* measure, lower ADC and IVIM-Dslow measures, increases imaging noises and decreases liver visibility. Young women have high liver T1rho value and then decrease substantially, while liver T1rho in men remains relatively unchanged with aging. In positron emission tomography (PET) studies, aging is associated with an increase of both liver fluorine-18-fluorodeoxyglucose maximum standard uptake and mean standard uptake values.
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Affiliation(s)
- Yì Xiáng J Wáng
- Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, China
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Wang J, Wu AH, Stanczyk FZ, Porcel J, Noureddin M, Terrault NA, Wilkens LR, Setiawan VW. Associations Between Reproductive and Hormone-Related Factors and Risk of Nonalcoholic Fatty Liver Disease in a Multiethnic Population. Clin Gastroenterol Hepatol 2021; 19:1258-1266.e1. [PMID: 32801014 PMCID: PMC7878579 DOI: 10.1016/j.cgh.2020.08.012] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 08/04/2020] [Accepted: 08/09/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Despite apparent differences between men and women in the prevalence and incidence of nonalcoholic fatty liver disease (NAFLD), there are limited epidemiologic data regarding the associations of reproductive and hormone-related factors with NAFLD. We examined the associations of these factors and exogenous hormone use with NAFLD risk in African American, Japanese American, Latino, Native Hawaiian, and white women. METHODS We conducted a nested case-control study (1861 cases and 17,664 controls) in the Multiethnic Cohort Study. NAFLD cases were identified using Medicare claims data; controls were selected among participants without liver disease and individually matched to cases by birth year, ethnicity, and length of Medicare enrollment. Reproductive and hormone-related factors and covariates were obtained from the baseline questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs. RESULTS Later age at menarche was associated inversely with NAFLD (Ptrend = .01). Parity, regardless of number of children or age at first birth, was associated with increased risk of NAFLD (OR, 1.25; 95% CI, 1.05-1.48). Oral contraceptive use also was linked to increased risk of NAFLD (OR, 1.14; 95% CI, 1.01-1.29; duration of use Ptrend = .04). Compared with women with natural menopause, those with oophorectomy (OR, 1.41; 95% CI, 1.18-1.68) or hysterectomy (OR, 1.33; 95% CI, 1.11-1.60) had an increased risk of NAFLD. A longer duration of menopause hormone therapy (only estrogen therapy) was linked with an increasing risk of NAFLD (OR per 5 years of use, 1.08, 95% CI, 1.01-1.15). CONCLUSIONS Findings from a large multiethnic study support the concept that menstrual and reproductive factors, as well as the use of exogenous hormones, are associated with the risk of NAFLD.
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Affiliation(s)
- Jun Wang
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA,Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
| | - Anna H. Wu
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA,Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
| | - Frank Z. Stanczyk
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA,Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Jacqueline Porcel
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Mazen Noureddin
- Division of Gastroenterology and Hepatology, Department of Medicine, and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Norah A. Terrault
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Lynne R. Wilkens
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI
| | - Veronica Wendy Setiawan
- Department of Preventive Medicine; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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Yang M, Ma F, Guan M. Role of Steroid Hormones in the Pathogenesis of Nonalcoholic Fatty Liver Disease. Metabolites 2021; 11:metabo11050320. [PMID: 34067649 PMCID: PMC8156407 DOI: 10.3390/metabo11050320] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/10/2021] [Accepted: 05/12/2021] [Indexed: 01/10/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and may progress to cirrhosis or even hepatocellular carcinoma. A number of steroid hormones are important regulators of lipid homeostasis through fine tuning the expression of genes related to lipid synthesis, export, and metabolism. Dysregulation of such pathways has been implicated in the pathogenesis of NAFLD. The aim of this review is to clarify the potential impact of steroid hormones on NAFLD. We also highlight potential interventions through modulating steroid hormone levels or the activities of their cognate receptors as therapeutic strategies for preventing NAFLD.
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Affiliation(s)
- Meng Yang
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Biochemistry and Molecular Biology, Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China;
- Center for Human Tissues and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China;
| | - Feng Ma
- Center for Human Tissues and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China;
| | - Min Guan
- Center for Human Tissues and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China;
- Correspondence: ; Tel.: +86-755-86585232
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Effects of Long-Term DHA Supplementation and Physical Exercise on Non-Alcoholic Fatty Liver Development in Obese Aged Female Mice. Nutrients 2021; 13:nu13020501. [PMID: 33546405 PMCID: PMC7913512 DOI: 10.3390/nu13020501] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/22/2021] [Accepted: 01/26/2021] [Indexed: 02/06/2023] Open
Abstract
Obesity and aging are associated to non-alcoholic fatty liver disease (NAFLD) development. Here, we investigate whether long-term feeding with a docosahexaenoic acid (DHA)-enriched diet and aerobic exercise, alone or in combination, are effective in ameliorating NAFLD in aged obese mice. Two-month-old female C57BL/6J mice received control or high fat diet (HFD) for 4 months. Then, the diet-induced obese (DIO) mice were distributed into four groups: DIO, DIO + DHA (15% dietary lipids replaced by a DHA-rich concentrate), DIO + EX (treadmill running), and DIO + DHA + EX up to 18 months. The DHA-rich diet reduced liver steatosis in DIO mice, decreasing lipogenic genes (Dgat2, Scd1, Srebp1c), and upregulated lipid catabolism genes (Hsl/Acox) expression. A similar pattern was observed in the DIO + EX group. The combination of DHA + exercise potentiated an increase in Cpt1a and Ppara genes, and AMPK activation, key regulators of fatty acid oxidation. Exercise, alone or in combination with DHA, significantly reversed the induction of proinflammatory genes (Mcp1, Il6, Tnfα, Tlr4) in DIO mice. DHA supplementation was effective in preventing the alterations induced by the HFD in endoplasmic reticulum stress-related genes (Ern1/Xbp1) and autophagy markers (LC3II/I ratio, p62, Atg7). In summary, long-term DHA supplementation and/or exercise could be helpful to delay NAFLD progression during aging in obesity.
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50
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Wang YM, Zhu KF, Zhou WJ, Zhang Q, Deng DF, Yang YC, Lu WW, Xu J, Yang YM. Sarcopenia is associated with the presence of nonalcoholic fatty liver disease in Zhejiang Province, China: a cross-sectional observational study. BMC Geriatr 2021; 21:55. [PMID: 33446095 PMCID: PMC7807816 DOI: 10.1186/s12877-020-01910-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
Background Currently, both non-alcoholic fatty liver disease (NAFLD) and sarcopenia have attracted extensive attention in public health. However, the relationship between NAFLD and sarcopenia remains unclear. This study aimed to clarify the sex-specific association between sarcopenia and NAFLD according to the Asian Working Group for Sarcopenia (AWGS). Methods Dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography were measured in 578 participants (92 men and 486 women) during their annual health examinations. Multivariate logistic regression models were used to explore the association between NAFLD and sarcopenia with its two components. Results A total of 154 participants (30 men and 124 women) had NAFLD. The prevalence of sarcopenia was higher among the participants with NAFLD than among those without NAFLD (men: 20.0% vs. 9.7%, P = 0.295, women: 15.3% vs. 8.0%, P = 0.019). Low muscle mass (LMM) was independently associated with NAFLD in both men and women (men: odds ratio [OR], 2.88; 95% confidence interval [CI] 1.52–5.46; women: OR, 2.08; 95% CI 1.63–2.67). However, low muscle strength (LMS) was independently associated with NAFLD only in male participants, with an OR of 1.15 (95% CI 1.02–1.28). Conclusion The occurrence of sarcopenia was associated with a higher risk of NAFLD, especially in men, as demonstrated by lower muscle mass and lower muscle strength.
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Affiliation(s)
- Yu-Ming Wang
- Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.,Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Ke-Fu Zhu
- Department of Cardiology, Zhejiang Hospital, Hangzhou, 310013, Zhejiang, China
| | - Wen-Jing Zhou
- Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.,Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Qin Zhang
- Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.,Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Dan-Feng Deng
- Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.,Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Yi-Chen Yang
- Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.,Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Wen-Wen Lu
- Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.,Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Jia Xu
- Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.,Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Yun-Mei Yang
- Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China. .,Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.
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